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Hearing Disorders: HELP
Articles by Hossein Najmabadi
Based on 31 articles published since 2010
(Why 31 articles?)
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Between 2010 and 2020, H. Najmabadi wrote the following 31 articles about Hearing Disorders.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review. 2016

Beheshtian, Maryam / Babanejad, Mojgan / Azaiez, Hela / Bazazzadegan, Niloofar / Kolbe, Diana / Sloan-Heggen, Christina / Arzhangi, Sanaz / Booth, Kevin / Mohseni, Marzieh / Frees, Kathy / Azizi, Mohammad Hossein / Daneshi, Ahmad / Farhadi, Mohammad / Kahrizi, Kimia / Smith, Richard Jh / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. · Academy of Medical Sciences Islamic Republic of Iran, Tehran, Iran. · Head and Neck Surgery Department and Research Center, Iran University of Medical Sciences, Tehran, Iran. ·Arch Iran Med · Pubmed #27743438.

ABSTRACT: A significant contribution to the causes of hereditary hearing impairment comes from genetic factors. More than 120 genes and 160 loci have been identified to be involved in hearing impairment. Given that consanguine populations are more vulnerable to most inherited diseases, such as hereditary hearing loss (HHL), the genetic picture of HHL among the Iranian population, which consists of at least eight ethnic subgroups with a high rate of intermarriage, is expected to be highly heterogeneous. Using an electronic literature review through various databases such as PubMed, MEDLINE, and Scopus, we review the current picture of HHL in Iran. In this review, we present more than 39 deafness genes reported to cause non-syndromic HHL in Iran, of which the most prevalent causative genes include GJB2, SLC26A4, MYO15A, and MYO7A. In addition, we highlight some of the more common genetic causes of syndromic HHL in Iran. These results are of importance for further investigation and elucidation of the molecular basis of HHL in Iran and also for developing a national diagnostic tool tailored to the Iranian context enabling early and efficient diagnosis of hereditary hearing impairment.

2 Review Genetics of non-syndromic hearing loss in the Middle East. 2014

Najmabadi, Hossein / Kahrizi, Kimia. ·Genetics Research Centre (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Electronic address: hnajm12@yahoo.com. · Genetics Research Centre (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Int J Pediatr Otorhinolaryngol · Pubmed #25281338.

ABSTRACT: Hearing impairment is the most common sensory disorder, present 1 in every 500 newborns. About 80% of genetic HL is classified as non-syndromic deafness. To date, over 115 non-syndromic loci have been identified of which fifty associated with autosomal recessive non-syndromic hearing loss (ARNSHL). In this review article, we represent the 40 genes function and contribution to genetic deafness in different Middle Eastern populations as well as gene frequencies and mutation spectrum. The wide variety of mutations have so far detected in 19 countries reflects the heterogeneity of the genes involved in HL in this region. The deafness genes can cause dysfunction of cochlear homeostasis, cellular organization, neuronal transmission, cell growth, differentiation, and survival, some coding for tectorial membrane-associated proteins, and the remaining with unknown functions. Non-syndromic deafness is highly heterogeneous and mutations in the GJB2 are responsible for almost 30-50% in northwest to as low as 0-5% in south and southeast of the Middle East, it remain as major gene in ARNSHL in Middle East. The other genes contributing to AR/ADNSHL in some countries have been determined while for many other countries in the Middle East have not been studied or little study has been done. With the advancement of next generation sequencing one could expect in next coming year many of the remaining genes to be determine and to understand their function in the inner ear.

3 Review Two Iranian families with a novel mutation in GJB2 causing autosomal dominant nonsyndromic hearing loss. 2011

Bazazzadegan, Niloofar / Sheffield, Abraham M / Sobhani, Masoomeh / Kahrizi, Kimia / Meyer, Nicole C / Van Camp, Guy / Hilgert, Nele / Abedini, Seyedeh Sedigheh / Habibi, Farkhondeh / Daneshi, Ahmad / Nishimura, Carla / Avenarius, Matthew R / Farhadi, Mohammad / Smith, Richard J H / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Am J Med Genet A · Pubmed #21484990.

ABSTRACT: Mutations in GJB2, encoding connexin 26 (Cx26), cause both autosomal dominant and autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNA3 and DFNB1 loci, respectively. Most of the over 100 described GJB2 mutations cause ARNSHL. Only a minority has been associated with autosomal dominant hearing loss. In this study, we present two families with autosomal dominant nonsyndromic hearing loss caused by a novel mutation in GJB2 (p.Asp46Asn). Both families were ascertained from the same village in northern Iran consistent with a founder effect. This finding implicates the D46N missense mutation in Cx26 as a common cause of deafness in this part of Iran mandating mutation screening of GJB2 for D46N in all persons with hearing loss who originate from this geographic region.

4 Article Novel mutations in MYTH4-FERM domains of myosin 15 are associated with autosomal recessive nonsyndromic hearing loss. 2019

Mehregan, Hoda / Mohseni, Marzieh / Jalalvand, Khadijeh / Arzhangi, Sanaz / Nikzat, Nooshin / Banihashemi, Sussan / Kahrizi, Kimia / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Electronic address: hnajm12@yahoo.com. ·Int J Pediatr Otorhinolaryngol · Pubmed #30579064.

ABSTRACT: OBJECTIVE: Hereditary hearing loss is the most common neurosensory disorder in humans caused by myriad mutations in numerous genes. Autosomal recessive nonsyndromic hearing loss (ARNSHL) accounts for 80% of hearing impairments of genetic origin and is quite prevalent in societies with a high rate of consanguinity. In the current study, we investigated the causes of sensorineural hearing loss in 24 unrelated Iranian families who were mainly consanguineous and had at least two affected children. METHODS: All probands were initially screened for GJB2 mutations, as the most common causes of ARNSHL in Iran. Verified GJB2-negative samples were subsequently subjected to whole exome sequencing (WES) to identify the underlying causes of hearing impairment, and the variants identified in each family were further confirmed by Sanger sequencing. RESULTS: WES revealed three previously unreported mutations in MYO15A, the gene encoding the unconventional myosin 15 (Myo15). All variants identified, c.C6436T (p.R2146W), c.C9584G (p.P3195R) and c.G10266C (p.Q3422H), reside in the MYTH4 (myosin tail homology) and FERM (4.1 ezrin, radixin, moesin) domains of the protein. CONCLUSION: Globally, mutations in MYO15A are considered to be among the most prevalent genetic causes of ARNSHL, and they rank as the third leading cause of hearing loss in the Iranian population, below GJB2 and SLC26A4. Yet again, these results endorse the importance of MYO15 screening in hearing impaired populations, particularly in Iran.

5 Article Grxcr2 is required for stereocilia morphogenesis in the cochlea. 2018

Avenarius, Matthew R / Jung, Jae-Yun / Askew, Charles / Jones, Sherri M / Hunker, Kristina L / Azaiez, Hela / Rehman, Atteeq U / Schraders, Margit / Najmabadi, Hossein / Kremer, Hannie / Smith, Richard J H / Géléoc, Gwenaëlle S G / Dolan, David F / Raphael, Yehoash / Kohrman, David C. ·Department of Otolaryngology/Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, Michigan, United States of America. · Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America. · Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia, United States of America. · Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. · Department of Communication Sciences and Disorders, East Carolina University, Greenville, North Carolina, United States of America. · Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America. · Section on Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland, United States of America. · Hearing & Genes Division, Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands. · Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·PLoS One · Pubmed #30157177.

ABSTRACT: Hearing and balance depend upon the precise morphogenesis and mechanosensory function of stereocilia, the specialized structures on the apical surface of sensory hair cells in the inner ear. Previous studies of Grxcr1 mutant mice indicated a critical role for this gene in control of stereocilia dimensions during development. In this study, we analyzed expression of the paralog Grxcr2 in the mouse and evaluated auditory and vestibular function of strains carrying targeted mutations of the gene. Peak expression of Grxcr2 occurs during early postnatal development of the inner ear and GRXCR2 is localized to stereocilia in both the cochlea and in vestibular organs. Homozygous Grxcr2 deletion mutants exhibit significant hearing loss by 3 weeks of age that is associated with developmental defects in stereocilia bundle orientation and organization. Despite these bundle defects, the mechanotransduction apparatus assembles in relatively normal fashion as determined by whole cell electrophysiological evaluation and FM1-43 uptake. Although Grxcr2 mutants do not exhibit overt vestibular dysfunction, evaluation of vestibular evoked potentials revealed subtle defects of the mutants in response to linear accelerations. In addition, reduced Grxcr2 expression in a hypomorphic mutant strain is associated with progressive hearing loss and bundle defects. The stereocilia localization of GRXCR2, together with the bundle pathologies observed in the mutants, indicate that GRXCR2 plays an intrinsic role in bundle orientation, organization, and sensory function in the inner ear during development and at maturity.

6 Article Old gene, new phenotype: splice-altering variants in 2018

Booth, Kevin T / Kahrizi, Kimia / Najmabadi, Hossein / Azaiez, Hela / Smith, Richard Jh. ·Molecular Otolaryngology Renal Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City, Iowa, USA. · The Interdisciplinary Graduate Program in Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Islamic Republic of Iran. ·J Med Genet · Pubmed #29703829.

ABSTRACT: BACKGROUND: Hearing loss is a genetically and phenotypically heterogeneous disorder. OBJECTIVES: The purpose of this study was to determine the genetic cause underlying the postlingual progressive hearing loss in two Iranian families. METHODS: We used OtoSCOPE, a next-generation sequencing platform targeting >150 genes causally linked to deafness, to screen two deaf probands. Data analysis was completed using a custom bioinformatics pipeline, and variants were functionally assessed using minigene splicing assays. RESULTS: We identified two homozygous splice-altering variants (c.37G>T and c.662-1G>C) in the CONCLUSIONS: These results suggest that loss-of-function mutations in

7 Article CDC14A phosphatase is essential for hearing and male fertility in mouse and human. 2018

Imtiaz, Ayesha / Belyantseva, Inna A / Beirl, Alisha J / Fenollar-Ferrer, Cristina / Bashir, Rasheeda / Bukhari, Ihtisham / Bouzid, Amal / Shaukat, Uzma / Azaiez, Hela / Booth, Kevin T / Kahrizi, Kimia / Najmabadi, Hossein / Maqsood, Azra / Wilson, Elizabeth A / Fitzgerald, Tracy S / Tlili, Abdelaziz / Olszewski, Rafal / Lund, Merete / Chaudhry, Taimur / Rehman, Atteeq U / Starost, Matthew F / Waryah, Ali M / Hoa, Michael / Dong, Lijin / Morell, Robert J / Smith, Richard J H / Riazuddin, Sheikh / Masmoudi, Saber / Kindt, Katie S / Naz, Sadaf / Friedman, Thomas B. ·Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. · School of Biological Sciences, University of the Punjab, Lahore 54590, Pakistan. · Section on Sensory Cell Development and Function, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. · Laboratory of Molecular and Cellular Neurobiology, Section on Molecular and Cellular Signaling, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. · Laboratoire Procédés de Criblage Moléculaire et Cellulaire, Centre de Biotechnologie de Sfax, Université de Sfax, Sfax 3451, Tunisia. · Center of Excellence in Molecular Biology, University of the Punjab, Lahore 54590, Pakistan. · Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology - Head and Neck Surgery, University of Iowa, Iowa City, 52242, IA, USA. · The Interdisciplinary Graduate Program in Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, 52242, IA, USA. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 1987513834, Iran. · Mouse Auditory Testing Core Facility, NIH, Bethesda, MD 20892, USA. · Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. · Division of Veterinary Resources, National Institutes of Health, Bethesda, MD 20892, USA. · Genetic Engineering Core, National Eye Institute, NIH, Bethesda, MD 20892, USA. · Genomics and Computational Biology Core, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA. · Pakistan Institute of Medical Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan. · Laboratory for Research in Genetic Diseases, Burn Centre, Allama Iqbal Medical College, University of Health Sciences, Lahore 54590, Pakistan. ·Hum Mol Genet · Pubmed #29293958.

ABSTRACT: The Cell Division-Cycle-14 gene encodes a dual-specificity phosphatase necessary in yeast for exit from mitosis. Numerous disparate roles of vertebrate Cell Division-Cycle-14 (CDC14A) have been proposed largely based on studies of cultured cancer cells in vitro. The in vivo functions of vertebrate CDC14A are largely unknown. We generated and analyzed mutations of zebrafish and mouse CDC14A, developed a computational structural model of human CDC14A protein and report four novel truncating and three missense alleles of CDC14A in human families segregating progressive, moderate-to-profound deafness. In five of these families segregating pathogenic variants of CDC14A, deaf males are infertile, while deaf females are fertile. Several recessive mutations of mouse Cdc14a, including a CRISPR/Cas9-edited phosphatase-dead p.C278S substitution, result in substantial perinatal lethality, but survivors recapitulate the human phenotype of deafness and male infertility. CDC14A protein localizes to inner ear hair cell kinocilia, basal bodies and sound-transducing stereocilia. Auditory hair cells of postnatal Cdc14a mutants develop normally, but subsequently degenerate causing deafness. Kinocilia of germ-line mutants of mouse and zebrafish have normal lengths, which does not recapitulate the published cdc14aa knockdown morphant phenotype of short kinocilia. In mutant male mice, degeneration of seminiferous tubules and spermiation defects result in low sperm count, and abnormal sperm motility and morphology. These findings for the first time define a new monogenic syndrome of deafness and male infertility revealing an absolute requirement in vivo of vertebrate CDC14A phosphatase activity for hearing and male fertility.

8 Article SLC52A2 mutations cause SCABD2 phenotype: A second report. 2018

Babanejad, Mojgan / Adeli, Omid Ali / Nikzat, Nooshin / Beheshtian, Maryam / Azarafra, Hakimeh / Sadeghnia, Farnaz / Mohseni, Marzieh / Najmabadi, Hossein / Kahrizi, Kimia. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Lorestan University of Medical Sciences, Khorramabad, Lorestan, Iran. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Electronic address: kkahrizi@uswr.ac.ir. ·Int J Pediatr Otorhinolaryngol · Pubmed #29287867.

ABSTRACT: INTRODUCTION: Autosomal recessive cerebellar ataxias (ARCAs) are a large group of neurodegenerative disorders that manifest mainly in children and young adults. Most ARCAs are heterogeneous with respect to age at onset, severity of disease progression, and frequency of extracerebellar and systemic signs. METHODS: The phenotype of a consanguineous Iranian family was characterized using clinical testing and pedigree analysis. Whole-exome sequencing was used to identify the disease-causing gene in this family. RESULTS AND CONCLUSION: Using whole exome sequencing (WES), a novel missense mutation in SLC52A2 gene is reported in a consanguineous Iranian family with progressive severe hearing loss, optic atrophy and ataxia. This is the second report of the genotype-phenotype correlation between this syndrome named spinocerebellar ataxia with blindness and deafness type 2 (SCABD2) and SLC52A2 gene.

9 Article Variants in CIB2 cause DFNB48 and not USH1J. 2018

Booth, K T / Kahrizi, K / Babanejad, M / Daghagh, H / Bademci, G / Arzhangi, S / Zareabdollahi, D / Duman, D / El-Amraoui, A / Tekin, M / Najmabadi, H / Azaiez, H / Smith, R J. ·Department of Otolaryngology, Head and Neck Surgery, Molecular Otolaryngology and Renal Research Laboratories, University of Iowa, Iowa City, IA, USA. · Interdisciplinary Graduate Program in Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, USA. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. · Division of Pediatric Genetics, Ankara University School of Medicine, Ankara, Turkey. · Institut Pasteur, Génétique et Physiologie de l'Audition, Paris, France. · John P. Hussman Institute for Human Genomics, Dr. John T. Macdonald Foundation Department of Human Genetics, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. ·Clin Genet · Pubmed #29112224.

ABSTRACT: The genetic, mutational and phenotypic spectrum of deafness-causing genes shows great diversity and pleiotropy. The best examples are the group of genes, which when mutated can either cause non-syndromic hearing loss (NSHL) or the most common dual sensory impairment, Usher syndrome (USH). Variants in the CIB2 gene have been previously reported to cause hearing loss at the DFNB48 locus and deaf-blindness at the USH1J locus. In this study, we characterize the phenotypic spectrum in a multiethnic cohort with autosomal recessive non-syndromic hearing loss (ARNSHL) due to variants in the CIB2 gene. Of the 6 families we ascertained, 3 segregated novel loss-of-function (LOF) variants, 2 families segregated missense variants (1 novel) and 1 family segregated a previously reported pathogenic variant in trans with a frameshift variant. This report is the first to show that biallelic LOF variants in CIB2 cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients. Here, we provide evidence disqualifying CIB2 as an USH-causing gene.

10 Article CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival. 2017

Michel, Vincent / Booth, Kevin T / Patni, Pranav / Cortese, Matteo / Azaiez, Hela / Bahloul, Amel / Kahrizi, Kimia / Labbé, Ménélik / Emptoz, Alice / Lelli, Andrea / Dégardin, Julie / Dupont, Typhaine / Aghaie, Asadollah / Oficjalska-Pham, Danuta / Picaud, Serge / Najmabadi, Hossein / Smith, Richard J / Bowl, Michael R / Brown, Steven Dm / Avan, Paul / Petit, Christine / El-Amraoui, Aziz. ·Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France. · Unité Mixte de Recherche- UMRS 1120, Institut National de la Santé et de la Recherche Médicale, Paris, France. · Sorbonne Universités, UPMC Univ Paris06, Paris, France. · Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology- Head and Neck Surgery, University of Iowa, Iowa City, Iowa. · Department of Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Retinal information processing - Pharmacology and Pathology, Institut de la Vision, Paris, France. · Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, Paris, France. · Mammalian Genetics Unit, MRC Harwell Institute, Oxford, UK. · Laboratoire de Biophysique Sensorielle, Faculté de Médecine, Biophysique Médicale, Centre Jean Perrin, Université d'Auvergne, Clermont-Ferrand, France. · Collège de France, Paris, France. · Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France aziz.el-amraoui@pasteur.fr. ·EMBO Mol Med · Pubmed #29084757.

ABSTRACT: Defects of CIB2, calcium- and integrin-binding protein 2, have been reported to cause isolated deafness, DFNB48 and Usher syndrome type-IJ, characterized by congenital profound deafness, balance defects and blindness. We report here two new nonsense mutations (pGln12* and pTyr110*) in

11 Article Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran. 2015

Sloan-Heggen, Christina M / Babanejad, Mojgan / Beheshtian, Maryam / Simpson, Allen C / Booth, Kevin T / Ardalani, Fariba / Frees, Kathy L / Mohseni, Marzieh / Mozafari, Reza / Mehrjoo, Zohreh / Jamali, Leila / Vaziri, Saeideh / Akhtarkhavari, Tara / Bazazzadegan, Niloofar / Nikzat, Nooshin / Arzhangi, Sanaz / Sabbagh, Farahnaz / Otukesh, Hasan / Seifati, Seyed Morteza / Khodaei, Hossein / Taghdiri, Maryam / Meyer, Nicole C / Daneshi, Ahmad / Farhadi, Mohammad / Kahrizi, Kimia / Smith, Richard J H / Azaiez, Hela / Najmabadi, Hossein. ·Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA. · Genetics Counseling Center, Kerman Welfare Institution, Kerman, Iran. · Division of Pediatric Nephrology, Hazrat-e-Ali Asghar Educational & Treatment Center, Iran University of Medical Sciences, Tehran, Iran. · Meybod Genetics Research Center, Shahid Fiazbakhsh Rehabilitation Comprehensive Center, Welfare Organization, Yazd, Iran. · Genetic Counseling Center, Shiraz Welfare Institution, Shiraz, Iran. · Head and Neck Surgery Department and Research Center, Iran University of Medical Sciences, Tehran, Iran. · Molecular Otolaryngology & Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, Iowa, USA. ·J Med Genet · Pubmed #26445815.

ABSTRACT: BACKGROUND: Countries with culturally accepted consanguinity provide a unique resource for the study of rare recessively inherited genetic diseases. Although hereditary hearing loss (HHL) is not uncommon, it is genetically heterogeneous, with over 85 genes causally implicated in non-syndromic hearing loss (NSHL). This heterogeneity makes many gene-specific types of NSHL exceedingly rare. We sought to define the spectrum of autosomal recessive HHL in Iran by investigating both common and rarely diagnosed deafness-causing genes. DESIGN: Using a custom targeted genomic enrichment (TGE) panel, we simultaneously interrogated all known genetic causes of NSHL in a cohort of 302 GJB2-negative Iranian families. RESULTS: We established a genetic diagnosis for 67% of probands and their families, with over half of all diagnoses attributable to variants in five genes: SLC26A4, MYO15A, MYO7A, CDH23 and PCDH15. As a reflection of the power of consanguinity mapping, 26 genes were identified as causative for NSHL in the Iranian population for the first time. In total, 179 deafness-causing variants were identified in 40 genes in 201 probands, including 110 novel single nucleotide or small insertion-deletion variants and three novel CNV. Several variants represent founder mutations. CONCLUSION: This study attests to the power of TGE and massively parallel sequencing as a diagnostic tool for the evaluation of hearing loss in Iran, and expands on our understanding of the genetics of HHL in this country. Families negative for variants in the genes represented on this panel represent an excellent cohort for novel gene discovery.

12 Article Two novel mutations in ILDR1 gene cause autosomal recessive nonsyndromic hearing loss in consanguineous Iranian families. 2015

Mehrjoo, Zohreh / Babanejad, Mojgan / Kahrizi, Kimia / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 1985713834, Iran. hnajm12@yahoo.com. ·J Genet · Pubmed #26440088.

ABSTRACT: -- No abstract --

13 Article PDZD7 and hearing loss: More than just a modifier. 2015

Booth, Kevin T / Azaiez, Hela / Kahrizi, Kimia / Simpson, Allen C / Tollefson, William T A / Sloan, Christina M / Meyer, Nicole C / Babanejad, Mojgan / Ardalani, Fariba / Arzhangi, Sanaz / Schnieders, Michael J / Najmabadi, Hossein / Smith, Richard J H. ·Department of Otolaryngology-Head Neck Surgery, Molecular Otolaryngology Renal Research Laboratories, University of Iowa, Iowa City, Iowa. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa. ·Am J Med Genet A · Pubmed #26416264.

ABSTRACT: Deafness is the most frequent sensory disorder. With over 90 genes and 110 loci causally implicated in non-syndromic hearing loss, it is phenotypically and genetically heterogeneous. Here, we investigate the genetic etiology of deafness in four families of Iranian origin segregating autosomal recessive non-syndromic hearing loss (ARNSHL). We used a combination of linkage analysis, homozygosity mapping, and a targeted genomic enrichment platform to simultaneously screen 90 known deafness-causing genes for pathogenic variants. Variant segregation was confirmed by Sanger sequencing. Linkage analysis and homozygosity mapping showed segregation with the DFNB57 locus on chromosome 10 in two families. Targeted genomic enrichment with massively parallel sequencing identified causal variants in PDZD7: a homozygous missense variant (p.Gly103Arg) in one family and compound heterozygosity for missense (p.Met285Arg) and nonsense (p.Tyr500Ter) variants in the second family. Screening of two additional families identified two more variants: (p.Gly228Arg) and (p.Gln526Ter). Variant segregation with the hearing loss phenotype was confirmed in all families by Sanger sequencing. The missense variants are predicted to be deleterious, and the two nonsense mutations produce null alleles. This report is the first to show that mutations in PDZD7 cause ARNSHL, a finding that offers addition insight into the USH2 interactome. We also describe a novel likely disease-causing mutation in CIB2 and illustrate the complexity associated with gene identification in diseases that exhibit large genetic and phenotypic heterogeneity.

14 Article Finding mutation within non-coding region of GJB2 reveals its importance in genetic testing of hearing loss in Iranian population. 2015

Kashef, Atie / Nikzat, Nooshin / Bazzazadegan, Niloofar / Fattahi, Zohreh / Sabbagh-Kermani, Farahnaz / Taghdiri, Maryam / Azadeh, Batool / Mojahedi, Faezeh / Khoshaeen, Atefeh / Habibi, Haleh / Najmabadi, Hossein / Kahrizi, Kimia. ·Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran; Deputy of Student Research, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. · Department of Genetic, Kerman Welfare Organization, Kerman, Iran. · Genetic Counseling Center, Shiraz Welfare Organization, Fars, Iran. · Welfare Counseling Center, Isfahan, Iran. · Mashhad Genetic Counseling Center, Mashhad, Khorasan, Iran. · Welfare Counseling Center, Mazandaran, Iran. · Genetic Counseling Center, Family Health Clinic, Mobasher Hospital, Hamedan, Iran. · Genetic Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. Electronic address: kahrizi@yahoo.com. ·Int J Pediatr Otorhinolaryngol · Pubmed #25555641.

ABSTRACT: OBJECTIVE: Hereditary hearing loss is the most common neurosensory disorder in humans. Half of the cases have genetic etiology with extraordinary genetic heterogeneity. Mutations in one gene, GJB2, are the most common cause for autosomal recessive non-syndromic hearing loss (ARNSHL) in many different populations. GJB2 encodes a gap junction channel protein (connexin 26), and is located on DFNB1 locus on chromosome 13q12.11 which also involve another connexin gene, GJB6. Mutation screening of GJB2 revealed that a high number of patients with deaf phenotype have heterozygous genotype and carry only one mutant allele. As the first comprehensive study in Iran, we have targeted GJB2-related Iranian heterozygotes, looking for second mutant allele which leads to hearing impairment. They bear first mutation in their coding exon of GJB2. METHOD: Using PCR-based direct sequencing, we assessed 103 patients with ARNSHL for variants in non-coding exon and promoter region of this gene, for the first time in Iran. RESULT: We have identified the second mutant allele in splice site of exon-1 of GJB2 which is known as IVS1+1G>A in 17 probands. We found no mutation in promoter region of GJB2. CONCLUSION: Our findings reveal that IVS1+1G>A mutation in noncoding exon of GJB2 is the most common mutation after 35delG within multi ethnical Iranian heterozygote samples. It emphasizes to approach exon1 of GJB2 in case of ARNSHL genetic diagnosis.

15 Article A novel mutation of the USH2C (GPR98) gene in an Iranian family with Usher syndrome type II. 2014

Kahrizi, Kimia / Bazazzadegan, Niloofar / Jamali, Leila / Nikzat, Nooshin / Kashef, Atie / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran 1985713834, Iran. hnajm12@yahoo.com. ·J Genet · Pubmed #25572244.

ABSTRACT: -- No abstract --

16 Article Investigation of ATP6V1B1 and ATP6V0A4 genes causing hereditary hearing loss associated with distal renal tubular acidosis in Iranian families. 2014

Zeinali, F / Mohseni, M / Fadaee, M / Fattahi, Z / Najmabadi, H / Otukesh, H / Kahrizi, K. ·Genetics Research Centre,University of Social Welfare and Rehabilitation Sciences,Tehran,Iran. · Department of Nephrology,Ali Asghar Children's Hospital,Tehran,Iran. ·J Laryngol Otol · Pubmed #25498251.

ABSTRACT: BACKGROUND: Hearing defects are the most common sensory disorders, affecting 1 out of every 500 newborns. ATP6V1B mutations are associated with early sensorineural hearing loss, whereas ATP6V0A4 mutations are classically associated with either late-onset sensorineural hearing loss or normal hearing. ATP6V1B1 and ATP6V0A4 genetic mutations cause recessive forms of distal renal tubular acidosis. METHOD: Ten unrelated deaf Iranian families with distal renal tubular acidosis were referred to the Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran. All exons of the ATP6V1B1 and ATP6V0A4 genes were sequenced in affected family members. RESULTS: We identified a previously reported ATP6V1B1 frameshift mutation (P385fsX441) in two families and a nucleotide substitution in exon 10 (P346R) in three families. In addition, one patient was homozygous for a novel nucleotide substitution in exon 3. CONCLUSION: ATP6V1B1 genetic mutations were detected in more than half of the families studied. Mutations in this gene therefore seem to be the most common causative factors in hearing loss associated with distal renal tubular acidosis in these families.

17 Article Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. 2014

Shearer, A Eliot / Eppsteiner, Robert W / Booth, Kevin T / Ephraim, Sean S / Gurrola, José / Simpson, Allen / Black-Ziegelbein, E Ann / Joshi, Swati / Ravi, Harini / Giuffre, Angelica C / Happe, Scott / Hildebrand, Michael S / Azaiez, Hela / Bayazit, Yildirim A / Erdal, Mehmet Emin / Lopez-Escamez, Jose A / Gazquez, Irene / Tamayo, Marta L / Gelvez, Nancy Y / Leal, Greizy Lopez / Jalas, Chaim / Ekstein, Josef / Yang, Tao / Usami, Shin-ichi / Kahrizi, Kimia / Bazazzadegan, Niloofar / Najmabadi, Hossein / Scheetz, Todd E / Braun, Terry A / Casavant, Thomas L / LeProust, Emily M / Smith, Richard J H. ·Molecular Otolaryngology & Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. · Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA. · Agilent Technologies, Cedar Creek, TX 78612, USA. · Epilepsy Research Centre, Department of Medicine, University of Melbourne, Heidelberg, VIC 3084, Australia. · Department of Otolaryngology, Faculty of Medicine, Medipol University, Istanbul 34083, Turkey. · Department of Medical Biology and Genetics, University of Mersin, Mersin 33160, Turkey. · Otology and Neurotology Group CTS495, Center for Genomic and Oncological Research (GENyO), Granada 18012, Spain. · Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá 11001000, Colombia. · Bonei Olam, Center for Rare Jewish Genetic Disorders, Brooklyn, NY 11204, USA. · Dor Yeshorim, The Committee for Prevention of Jewish Genetic Diseases, Brooklyn, NY 11211, USA. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, and the Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 20025, China. · Department of Otorhinolaryngology, School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan. · Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran 1985713834, Iran. · Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA; Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, IA 52242, USA; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA. · Molecular Otolaryngology & Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: richard-smith@uiowa.edu. ·Am J Hum Genet · Pubmed #25262649.

ABSTRACT: Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.

18 Article Identification of a founder mutation for Pendred syndrome in families from northwest Iran. 2014

Mohseni, Marzieh / Honarpour, Asal / Mozafari, Reza / Davarnia, Behzad / Najmabadi, Hossein / Kahrizi, Kimia. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran. · Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran. Electronic address: kahrizi@yahoo.com. ·Int J Pediatr Otorhinolaryngol · Pubmed #25239229.

ABSTRACT: OBJECTIVE: Mutations in the SLC26A4 gene cause both Pendred syndrome and autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB4 locus. The SLC26A4 mutations vary among different communities. Previous studies have shown that mutations in the SLC26A4 gene are responsible for the more common syndromic hereditary hearing loss in Iran. This study assesses the possibility of a founder mutation for Pendred syndrome in northwest Iran. MATERIALS AND METHODS: In this study, we performed comprehensive clinical and genetic evaluations in two unrelated families from northwest Iran with nine members affected by hearing loss (HL). After testing short tandem repeat (STR) markers to confirm linkage to the SLC26A4 locus, we screened the SLC26A4 gene by Sanger sequencing of all 21 exons, exon-intron boundaries and the promoter region for any causative mutation. We identified the same causative mutation in these two families as we had detected earlier in two other Azeri families from northwest Iran. To investigate the possibility of a founder effect in these four families, we conducted haplotype analysis, and 14 single nucleotide polymorphisms (SNPs) throughout the SLC26A4 gene were genotyped. RESULTS: Patients in the two families showed the phenotype of Pendred syndrome. A known frameshift mutation (c.965insA, p.N322Fs7X) in exon 8 was identified in the two families, which was the same mutation that we detected previously in two other Azeri families. The results of haplotype analysis showed that all 15 patients from four families shared the founder mutation. Common haplotypes were not observed in noncarrier members. CONCLUSIONS: Based on the results of our two studies, the c.965insA mutation has only been described in Iranian families from northwest Iran, so there is evidence for a founder mutation originating in this part of Iran.

19 Article A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. 2012

Babanejad, Mojgan / Fattahi, Zohreh / Bazazzadegan, Niloofar / Nishimura, Carla / Meyer, Nicole / Nikzat, Nooshin / Sohrabi, Elahe / Najmabadi, Amin / Jamali, Peyman / Habibi, Farkhonde / Smith, Richard J H / Kahrizi, Kimia / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Am J Med Genet A · Pubmed #22903915.

ABSTRACT: Hearing loss is the most common sensory disorder worldwide and affects 1 of every 500 newborns. In developed countries, at least 50% of cases are genetic, most often resulting in nonsyndromic deafness (70%), which is usually autosomal recessive (∼80%). Although the cause of hearing loss is heterogeneous, mutations in GJB2 gene at DFNB1 locus are the major cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. Our previous study showed that mutations of GJB2 gene do not contribute to the major genetic load of deafness in the Iranian population (∼16%). Therefore, to define the importance of other genes in contributing to an ARNSHL phenotype in the Iranian population, we used homozygosity mapping to identify regions of autozygosity-by-descent in 144 families which two or more progeny had ARNSHL but were negative for GJB2 gene mutations. Using flanking or intragenic short-tandem repeat markers for 33 loci we identified 33 different homozygous variations in 10 genes, of which 9 are novel. In aggregate, these data explain ∼40% of genetic background of ARNHSL in the Iranian population.

20 Article Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population. 2012

Fattahi, Zohreh / Shearer, A Eliot / Babanejad, Mojgan / Bazazzadegan, Niloofar / Almadani, Seyed Navid / Nikzat, Nooshin / Jalalvand, Khadijeh / Arzhangi, Sanaz / Esteghamat, Fatemehsadat / Abtahi, Rezvan / Azadeh, Batool / Smith, Richard J H / Kahrizi, Kimia / Najmabadi, Hossein. ·Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Am J Med Genet A · Pubmed #22736430.

ABSTRACT: MYO15A is located at the DFNB3 locus on chromosome 17p11.2, and encodes myosin-XV, an unconventional myosin critical for the formation of stereocilia in hair cells of cochlea. Recessive mutations in this gene lead to profound autosomal recessive nonsyndromic hearing loss (ARNSHL) in humans and the shaker2 (sh2) phenotype in mice. Here, we performed a study on 140 Iranian families in order to determine mutations causing ARNSHL. The families, who were negative for mutations in GJB2, were subjected to linkage analysis. Eight of these families showed linkage to the DFNB3 locus, suggesting a MYO15A mutation frequency of 5.71% in our cohort of Iranian population. Subsequent sequencing of the MYO15A gene led to identification of 7 previously unreported mutations, including 4 missense mutations, 1 nonsense mutation, and 2 deletions in different regions of the myosin-XV protein.

21 Article The spectrum of GJB2 mutations in the Iranian population with non-syndromic hearing loss--a twelve year study. 2012

Bazazzadegan, Niloofar / Nikzat, Nooshin / Fattahi, Zohreh / Nishimura, Carla / Meyer, Nicole / Sahraian, Shima / Jamali, Payman / Babanejad, Mojgan / Kashef, Atie / Yazdan, Hilda / Sabbagh Kermani, Farahnaz / Taghdiri, Maryam / Azadeh, Batool / Mojahedi, Faezeh / Khoshaeen, Atefeh / Habibi, Haleh / Reyhanifar, Farahnaz / Nouri, Narges / Smith, Richard J H / Kahrizi, Kimia / Najmabadi, Hossein. ·Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Int J Pediatr Otorhinolaryngol · Pubmed #22695344.

ABSTRACT: OBJECTIVE: Mutations in GJB2, encoding connexin 26 (CX26), are causally related to autosomal recessive form of non-syndromic hearing loss (NSHL) at the DFNB1 locus and autosomal dominant NSHL at the DFNA3 locus. In this study, we investigated the prevalence of GJB2 mutations in the Iranian deaf population. METHODS: A total of 2322 deaf probands presenting the ethnically diverse Iranian population were screened for variants in GJB2. All persons were first screened for the c.35delG mutation, as this variant is the most prevalent GJB2-deafness causing mutation in the Iranian population. In all persons carrying zero or one c.35delG allele, exons 1 and 2 were then sequenced. RESULTS: In total, 374 (~16%) families segregated GJB2-related deafness caused by 45 different mutations and 5 novel variants. The c.35delG mutation was most commonly identified and accounts for ~65% of the GJB2 mutations found in population studied. CONCLUSION: Our data also show that there is a gradual decrease in the frequency of the c.35delG mutation and of GJB2-related deafness in general in a cline across Iran extending from the northwest to southeast.

22 Article Two novel SLC26A4 mutations in Iranian families with autosomal recessive hearing loss. 2012

Yazdanpanahi, Nasrin / Chaleshtori, Morteza Hashemzadeh / Tabatabaiefar, Mohammad Amin / Noormohammadi, Zahra / Farrokhi, Effat / Najmabadi, Hossein / Shahbazi, Shirin / Hosseinipour, Azam. ·Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. nasrin232002@yahoo.com ·Int J Pediatr Otorhinolaryngol · Pubmed #22444735.

ABSTRACT: OBJECTIVE: Due to the fact that SLC26A4 has been suggested as the second cause of hearing loss (HL) in Iran as well as many other countries, obtaining more comprehensive information about SLC26A4 mutations can facilitate more efficient genetic services to the patients with hereditary hearing loss. This investigation aims to detect genetic cause of two Iranian families with hearing loss. METHODS: In the present study, genetic linkage analysis via 4 short tandem repeat markers linked to SLC26A4 was performed for two consanguineous families originating from Hormozgan and Chaharmahal va Bakhtiari provinces of Iran, co-segregating autosomal recessive hearing loss and showed no GJB2 mutations in our preliminary investigation. For identification of mutations, DNA sequencing of SLC26A4 including all the 21 exons, exon-intron boundaries and the promoter was carried out. RESULTS: The results showed linkage to this gene in both families. After sequencing, two novel SLC26A4 mutations (c.65-66insT in exon 2 and c.2106delG in exon 19) were revealed in the two studied families. CONCLUSION: Results of this study stress the necessity of considering the analysis of SLC26A4 in molecular diagnosis of deafness especially when phenotypes such as goiter or enlarged vestibular aqueduct are present.

23 Article Spectrum of GJB2 (Cx26) gene mutations in Iranian Azeri patients with nonsyndromic autosomal recessive hearing loss. 2012

Davarnia, Behzad / Babanejad, Mojgan / Fattahi, Zohreh / Nikzat, Nooshin / Bazazzadegan, Niloofar / Pirzade, Akbar / Farajollahi, Reza / Nishimura, Carla / Jalalvand, Khadijeh / Arzhangi, Sanaz / Kahrizi, Kimia / Smith, Richard J H / Najmabadi, Hossein. ·Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Int J Pediatr Otorhinolaryngol · Pubmed #22172221.

ABSTRACT: OBJECTIVE: Hereditary hearing impairment is a genetically heterogeneous disorder. In spite of this, mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries and are largely dependent on ethnic groups. The purpose of our study was to characterize the type and prevalence of GJB2 mutations among Azeri population of Iran. METHODS: Fifty families presenting autosomal recessive nonsyndromic hearing loss from Ardabil province of Iran were studied for mutations in GJB2 gene. All DNA samples were screened for c.35delG mutation by ARMS PCR. Samples from patients who were normal for c.35delG were analyzed for the other variations in GJB2 by direct sequencing. In the absence of mutation detection, GJB6 was screened for the del(GJB6-D13S1830) and del(GJB6-D13S1854). RESULT: Thirteen families demonstrated alteration in the Cx26 (26%). The 35delG mutation was the most common one, accounting for 69.2% (9 out of 13 families). All the detected families were homozygous for this mutation. Two families were homozygous for delE120 and 299-300delAT mutations. We also identified a novel mutation: c.463-464 delTA in 2 families resulting in a frame shift mutation. CONCLUSION: Our results suggest that c.35delG mutation in the GJB2 gene is the most important cause of GJB2 related deafness in Iranian Azeri population.

24 Article Did the GJB2 35delG mutation originate in Iran? 2011

Norouzi, Vahideh / Azizi, Hiva / Fattahi, Zohreh / Esteghamat, Fatemehsadat / Bazazzadegan, Niloofar / Nishimura, Carla / Nikzat, Nooshin / Jalalvand, Khadijeh / Kahrizi, Kimia / Smith, Richard J H / Najmabadi, Hossein. ·Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. ·Am J Med Genet A · Pubmed #21910243.

ABSTRACT: Mutations in GJB2 are a major cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in many populations. A single mutation of this gene (35delG) accounts for approximately 70% of GJB2 mutations that are associated with ARNSHL in Caucasians in many European countries and also in Iranian. In this study, we used PCR and restriction digestion to genotype five single nucleotide polymorphisms (SNPs) that define the genetic background of the 35delG mutation over an interval of 98 Kbp that includes the coding and flanking regions of GJB2. Two microsatellite markers, D13S175 and D13S141, were also analyzed in patients and controls. These data suggest that the 35delG mutation originated in northern Iran.

25 Article Prevalence of GJB2-associated deafness and outcomes of cochlear implantation in Iran. 2011

Daneshi, A / Hassanzadeh, S / Emamdjomeh, H / Mohammadi, S H / Arzhangi, S / Farhadi, M / Najmabadi, H. ·Head and Neck Surgery Department and Research Center, Iran University of Medical Sciences, Tehran, Iran. daneshi@daneshi.net ·J Laryngol Otol · Pubmed #21281533.

ABSTRACT: OBJECTIVES: To investigate the prevalence of mutations in the coding exon of the GJB2 gene in Iranian children with cochlear implants, and to compare the outcomes of auditory perception and speech production in cochlear-implanted children with and without GJB2 mutation. MATERIALS AND METHODS: One hundred and sixty-six prelingually deaf children who had undergone cochlear implantation at the Iranian Cochlear Implant Center, Tehran, were selected from a pool of 428 implanted children. The prevalence of GJB2 gene mutations was assessed using nested polymerase chain reaction and direct sequencing. To enable comparisons, we also identified 36 implanted children with non-GJB2 deafness. Patients' speech perception and speech production were assessed using the Categorization of Auditory Performance and Speech Intelligibility Rating scales. RESULTS: Thirty-three of 166 probands (19.9 per cent) were found to have GJB2 deafness-causing allele variants and were diagnosed with DFNB1 deafness. Results also indicated a significant improvement in speech perception and production scores in both GJB2 and non-GJB2 patients over time. CONCLUSION: Children with GJB2-related deafness benefit from cochlear implantation to the same extent as those with non-GJB2-related deafness.

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