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Hearing Disorders: HELP
Articles by Lisa S. Nolan
Based on 7 articles published since 2010
(Why 7 articles?)

Between 2010 and 2020, L. Nolan wrote the following 7 articles about Hearing Disorders.
+ Citations + Abstracts
1 Clinical Trial A functional and genetic analysis of SOD2 promoter variants and their contribution to age-related hearing loss. 2013

Nolan, Lisa S / Cadge, Barbara A / Gomez-Dorado, Miriam / Dawson, Sally J. ·Centre for Auditory Research, Ear Institute, University College London, 332 Gray's Inn Road, London WC1X 8EE, UK. ·Mech Ageing Dev · Pubmed #23500038.

ABSTRACT: METHODS: Putative regulatory variants identified in the SOD2 promoter using bioinformatics were functionally evaluated in an inner-ear-derived cell line (OC-2). Variants with effects on transcription factor binding were then tested in association studies in discovery and replication cohorts (London ARHL and ELSA cohorts, n=2177). RESULTS: The rs5746092 (-38C>G) and rs2758343 (-299C>A) SNPs alter the affinity of the SOD2 promoter for AP-2α and SP1 respectively. Evidence of an association between the -38C>G SNP and ARHL was detected in the London cohort only; p=0.0436, OR=1.35 [1.05-1.73]. This effect was strongest in males reporting family history of ARHL (p=0.0095) and was independent of reported noise exposure. The rs2758343 (-299C>A) rSNP was found to be in complete LD with the well characterised functional variant rs4880 (Ala16Val) and was not associated with hearing loss. CONCLUSION: This study describes the effect of common SOD2 promoter variation on SOD2 promoter regulation and links it to ARHL risk in men. However, due to lack of replication, this association should be regarded as suggestive only.

2 Article Whole exome sequencing in adult-onset hearing loss reveals a high load of predicted pathogenic variants in known deafness-associated genes and identifies new candidate genes. 2018

Lewis, Morag A / Nolan, Lisa S / Cadge, Barbara A / Matthews, Lois J / Schulte, Bradley A / Dubno, Judy R / Steel, Karen P / Dawson, Sally J. ·Wolfson Centre for Age-Related Diseases, King's College London, WC2R 2LS, London, UK. · Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. · UCL Ear Institute, University College London, WC1X 8EE, London, UK. · Medical University of South Carolina, Charleston, SC, 29425, USA. · UCL Ear Institute, University College London, WC1X 8EE, London, UK. sally.dawson@ucl.ac.uk. ·BMC Med Genomics · Pubmed #30180840.

ABSTRACT: BACKGROUND: Deafness is a highly heterogenous disorder with over 100 genes known to underlie human non-syndromic hearing impairment. However, many more remain undiscovered, particularly those involved in the most common form of deafness: adult-onset progressive hearing loss. Despite several genome-wide association studies of adult hearing status, it remains unclear whether the genetic architecture of this common sensory loss consists of multiple rare variants each with large effect size or many common susceptibility variants each with small to medium effects. As next generation sequencing is now being utilised in clinical diagnosis, our aim was to explore the viability of diagnosing the genetic cause of hearing loss using whole exome sequencing in individual subjects as in a clinical setting. METHODS: We performed exome sequencing of thirty patients selected for distinct phenotypic sub-types from well-characterised cohorts of 1479 people with adult-onset hearing loss. RESULTS: Every individual carried predicted pathogenic variants in at least ten deafness-associated genes; similar findings were obtained from an analysis of the 1000 Genomes Project data unselected for hearing status. We have identified putative causal variants in known deafness genes and several novel candidate genes, including NEDD4 and NEFH that were mutated in multiple individuals. CONCLUSIONS: The high frequency of predicted-pathogenic variants detected in known deafness-associated genes was unexpected and has significant implications for current diagnostic sequencing in deafness. Our findings suggest that in a clinic setting, efforts should be made to a) confirm key sequence results by Sanger sequencing, b) assess segregations of variants and phenotypes within the family if at all possible, and c) use caution in applying current pathogenicity prediction algorithms for diagnostic purposes. We conclude that there may be a high number of pathogenic variants affecting hearing in the ageing population, including many in known deafness-associated genes. Our findings of frequent predicted-pathogenic variants in both our hearing-impaired sample and in the larger 1000 Genomes Project sample unselected for auditory function suggests that the reference population for interpreting variants for this very common disorder should be a population of people with good hearing for their age rather than an unselected population.

3 Article Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay. 2016

Schilit, Samantha Lp / Currall, Benjamin B / Yao, Ruen / Hanscom, Carrie / Collins, Ryan L / Pillalamarri, Vamsee / Lee, Dong-Young / Kammin, Tammy / Zepeda-Mendoza, Cinthya J / Mononen, Tarja / Nolan, Lisa S / Gusella, James F / Talkowski, Michael E / Shen, Jun / Morton, Cynthia C. ·Department of Genetics, Harvard Medical School, Boston, MA, USA. · Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA. · Harvard Medical School, Boston, MA, USA. · Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA. · Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. · Department of Clinical Genetics, Kuopio University Hospital, Kuopio, Finland. · UCL Ear Institute, University College London, London, UK. · Medical and Population Genetics Program, Broad Institute, Cambridge, MA, USA. · Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. · Laboratory for Molecular Medicine, Partners Personalized Medicine, Partners HealthCare, Cambridge, MA, USA. · Manchester Academic Health Science Centre, University of Manchester, Manchester, UK. ·Eur J Hum Genet · Pubmed #27381092.

ABSTRACT: Analysis of chromosomal rearrangements has been highly successful in identifying genes involved in many congenital abnormalities including hearing loss. Herein, we report a subject, designated DGAP242, with congenital hearing loss (HL) and a de novo balanced translocation 46,XX,t(1;5)(q32;q15)dn. Using multiple next-generation sequencing techniques, we obtained high resolution of the breakpoints. This revealed disruption of the orphan receptor ESRRG on chromosome 1, which is differentially expressed in inner ear hair cells and has previously been implicated in HL, and disruption of KIAA0825 on chromosome 5. Given the translocation breakpoints and supporting literature, disruption of ESRRG is the most likely cause for DGAP242's phenotype and implicates ESRRG in a monogenic form of congenital HL, although a putative contributory role for KIAA0825 in the subject's disorder cannot be excluded.

4 Article Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss. 2015

Vuckovic, Dragana / Dawson, Sally / Scheffer, Deborah I / Rantanen, Taina / Morgan, Anna / Di Stazio, Mariateresa / Vozzi, Diego / Nutile, Teresa / Concas, Maria P / Biino, Ginevra / Nolan, Lisa / Bahl, Aileen / Loukola, Anu / Viljanen, Anne / Davis, Adrian / Ciullo, Marina / Corey, David P / Pirastu, Mario / Gasparini, Paolo / Girotto, Giorgia. ·Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34100, Italy. · UCL Ear Institute, University College London, London WC1X 8EE, UK. · Howard Hughes Medical Institute and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. · Gerontology Research Center and Department of Health Sciences, University of Jyväskylä, Jyväskylä FI-40014, Finland. · Institute for Maternal and Child Health IRCCS 'Burlo Garofolo', Trieste 34100, Italy. · Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, Naples 80131, Italy. · Institute of Population Genetics, National Research Council of Italy, Sassari 07100, Italy. · Institute of Molecular Genetics, National Research Council of Italy, Pavia 27100, Italy. · Department of Public Health, Hjelt Institute, University of Helsinki, Helsinki FI-00014, Finland and. · Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34100, Italy, Institute for Maternal and Child Health IRCCS 'Burlo Garofolo', Trieste 34100, Italy, Experimental Genetics Division, Sidra, Doha, Qatar. · Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34100, Italy, giorgia.girotto@burlo.trieste.it. ·Hum Mol Genet · Pubmed #26188009.

ABSTRACT: Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function.

5 Article Cochlear implantation in the mouse via the round window: effects of array insertion. 2014

Mistry, N / Nolan, L S / Saeed, S R / Forge, A / Taylor, R R. ·UCL Ear Institute, 332 Grays Inn Road, London WC1X 2EE, UK. Electronic address: nina.mistry.11@ucl.ac.uk. · UCL Ear Institute, 332 Grays Inn Road, London WC1X 2EE, UK. Electronic address: l.nolan@ucl.ac.uk. · UCL Ear Institute, 332 Grays Inn Road, London WC1X 2EE, UK. Electronic address: shakeel.saeed@ucl.ac.uk. · UCL Ear Institute, 332 Grays Inn Road, London WC1X 2EE, UK. Electronic address: a.forge@ucl.ac.uk. · UCL Ear Institute, 332 Grays Inn Road, London WC1X 2EE, UK. Electronic address: ruth.r.taylor@ucl.ac.uk. ·Hear Res · Pubmed #24657211.

ABSTRACT: Animal models are the only means of assessing the effects of cochlear implantation (CI) at a cellular and molecular level. The range of naturally occurring and genetically-modified mouse strains which mimic human deafness provide excellent opportunities for auditory research. To date, there are very few studies of CI in mice. The main aims of this study were to develop a reproducible and viable technique to enable long term CI in the mouse and to assess the response of the mouse cochlea to implantation as a means of evaluating the success of the procedure. Electrode array implantation via the round window was performed in C57Bl/6 mice aged 3 and 6 months. The contralateral cochlea acted as a control. Auditory brainstem responses (ABR) were recorded prior to and following CI. Analysis showed greater threshold shifts in the implanted ear compared to the control ear post-implantation, but substantial preservation of hearing. There were no cases in which implantation caused a profound hearing loss across all frequencies. Cone beam computerised tomography and light microscopy confirmed correct placement of the electrode array within the scala tympani. Cochleae were prepared for histological examination. Initial analysis revealed encapsulation of the implant in tissue with morphological characteristics suggestive of fibrosis. Our results show that mouse CI via the round window offers a model for exploring tissue responses to implantation.

6 Article Estrogen-related receptor gamma and hearing function: evidence of a role in humans and mice. 2013

Nolan, Lisa S / Maier, Hannes / Hermans-Borgmeyer, Irm / Girotto, Giorgia / Ecob, Russell / Pirastu, Nicola / Cadge, Barbara A / Hübner, Christian / Gasparini, Paolo / Strachan, David P / Davis, Adrian / Dawson, Sally J. ·UCL Ear Institute, University College London, London, UK. ·Neurobiol Aging · Pubmed #23540940.

ABSTRACT: Since estrogen is thought to protect pre-menopausal women from age-related hearing loss, we investigated whether variation in estrogen-signalling genes is linked to hearing status in the 1958 British Birth Cohort. This analysis implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult hearing function and was investigated further in a total of 6134 individuals in 3 independent cohorts: (i) the 1958 British Birth Cohort; (ii) a London ARHL case-control cohort; and (iii) a cohort from isolated populations of Italy and Silk Road countries. Evidence of an association between the minor allele of single nucleotide polymorphism (SNP) rs2818964 and hearing status was found in females, but not in males in 2 of these cohorts: p = 0.0058 (London ARHL) and p = 0.0065 (Carlantino, Italy). Furthermore, assessment of hearing in Esrrg knock-out mice revealed a mild 25-dB hearing loss at 5 weeks of age. At 12 weeks, average hearing thresholds in female mice((-/-)) were 15 dB worse than in males((-/-)). Together these data indicate ESRRG plays a role in maintenance of hearing in both humans and mice.

7 Minor Community network for deaf scientists. 2017

Adler, Henry J / Anbuhl, Kelsey L / Atcherson, Samuel R / Barlow, Nathan / Brennan, Marc A / Brigande, John V / Buran, Brad N / Fraenzer, Juergen-Theodor / Gale, Jonathan E / Gallun, Frederick J / Gluck, Sarah D / Goldsworthy, Ray L / Heng, Joseph / Hight, Ariel Edward / Huyck, Julia J / Jacobson, Barry D / Karasawa, Takatoshi / Kovačić, Damir / Lim, Stacey R / Malone, Alexander K / Nolan, Lisa S / Pisano, Dominic V / Rao, Valluri R M / Raphael, Robert M / Ratnanather, J Tilak / Reiss, Lina A J / Ruffin, Chad V / Schwalje, Adam T / Sinan, Moaz / Stahn, Patricia / Steyger, Peter S / Tang, Stephen J / Tejani, Viral D / Wong, Victor. ·Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214, USA. henryadl@buffalo.edu. · University of Colorado School of Medicine, Aurora, CO 80045, USA. · University of Arkansas at Little Rock, Little Rock, AR 72204, USA. · University of Auckland, Auckland 1072, New Zealand. · Boys Town National Research Hospital, Boys Town, NE 68010, USA. · Oregon Health & Science University, Portland, OR 97239, USA. · Max Rubner-Institut, 95326 Kulmbach, Germany. · University College London Ear Institute, London, WC1X 8EE, UK. · U.S. Department of Veterans Affairs, Portland, OR 97239, USA. · Harvard University, Cambridge, MA 02138, USA. · University of Southern California, Los Angeles, CA 90007, USA. · Johns Hopkins Hospital, Baltimore, MD 21287, USA. · Kent State University, Kent, OH 44240, USA. · Massachusetts Institute of Technology, Cambridge, MA 02139, USA. · Kyorin Pharmaceutical Co., Ltd., Tochigi 329-0114, Japan. · University of Split, 21000 Split, Croatia. · Central Michigan University, Mt. Pleasant, MI 48859, USA. · University of South Florida, Tampa, FL 33620, USA. · University of Michigan School of Medicine, Ann Arbor, MI 48103, USA. · Saratoga, CA 95070, USA. · Rice University, Houston, TX 77005, USA. · Johns Hopkins University, Baltimore, MD 21218, USA. · Indiana University School of Medicine, Indianapolis, IN 46202, USA. · University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. · Wayne State University School of Medicine, Detroit, MI 48201, USA. · Saarland University Faculty of Medicine, D-66421 Homburg, Germany. · University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA. · Burke Medical Research Institute, White Plains, NY 10605, USA. ·Science · Pubmed #28450605.

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