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Hearing Disorders: HELP
Articles by Uzma Shaukat
Based on 2 articles published since 2009
(Why 2 articles?)

Between 2009 and 2019, Uzma Shaukat wrote the following 2 articles about Hearing Disorders.
+ Citations + Abstracts
1 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.

2 Article Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome. 2011

Riazuddin, Saima / Ahmed, Zubair M / Hegde, Rashmi S / Khan, Shaheen N / Nasir, Idrees / Shaukat, Uzma / Riazuddin, Sheikh / Butman, John A / Griffith, Andrew J / Friedman, Thomas B / Choi, Byung Yoon. ·Laboratory of Molecular Genetics, Division of Pediatric Otolaryngology Head & Neck Surgery, Cincinnati Children's Hospital Research Foundation, and University of Cincinnati, College of Medicine, Cincinnati, OH, USA. ·BMC Med Genet · Pubmed #21306635.

ABSTRACT: BACKGROUND: Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia. METHODS: We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to FGF3 mutations. Ten affected individuals from three large Pakistani families segregating FGF3 mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations. RESULTS: Two families segregated reported mutations (p.R104X and p.R95W) and one family segregated a novel mutation (p.R132GfsX26) of FGF3. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced FGF10 as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of FGF3, otitis media, or a consequence of genetic background in these three family members. CONCLUSIONS: We noted a less prominent dental and external ear phenotype in association with the homozygous p.R95W. Therefore, we conclude that the manifestations of recessive FGF3 mutations range from fully penetrant LAMM syndrome to deafness with residual inner ear structures and, by extension, with minimal syndromic features, an observation with implications for cochlear implantation candidacy.