Journal article
Exome sequencing utility in defining the genetic landscape of hearing loss and novel-gene discovery in Iran
Clinical genetics, Vol.100(1), pp.59-78
07/2021
DOI: 10.1111/cge.13956
PMCID: PMC8195868
PMID: 33713422
Abstract
Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non-syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease-causing variants in known deafness-associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness-associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30% of our study cohort using ES. This study corroborates the observation that high-throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL.
Details
- Title: Subtitle
- Exome sequencing utility in defining the genetic landscape of hearing loss and novel-gene discovery in Iran
- Creators
- Marzieh Mohseni - University of Social Welfare and Rehabilitation SciencesMojgan Babanejad - University of Social Welfare and Rehabilitation SciencesKevin T Booth - Harvard UniversityPayman Jamali - Counseling CenterKhadijeh Jalalvand - University of Social Welfare and Rehabilitation SciencesBehzad Davarnia - Ardabil University of Medical SciencesFariba Ardalani - University of Social Welfare and Rehabilitation SciencesAtefeh Khoshaeen - Mehrgan Genetic Clinic, Sari, Iran.Sanaz Arzhangi - University of Social Welfare and Rehabilitation SciencesFatemeh Ghodratpour - University of Social Welfare and Rehabilitation SciencesMaryam Beheshtian - University of Social Welfare and Rehabilitation SciencesFaezeh Jahanshad - Navid's Institute of Infertility, Tehran, Iran.Hasan Otukesh - Iran University of Medical SciencesFatemeh Bahrami - University of Social Welfare and Rehabilitation SciencesSeyed Morteza Seifati - Islamic Azad University, TehranNiloofar Bazazzadegan - University of Social Welfare and Rehabilitation SciencesFarkhonde Habibi - Counseling CenterHanieh Behravan - University of Social Welfare and Rehabilitation SciencesSepide Mirzaei - University of Social Welfare and Rehabilitation SciencesFatemeh Keshavarzi - University of Social Welfare and Rehabilitation SciencesNooshin Nikzat - University of Social Welfare and Rehabilitation SciencesZohreh Mehrjoo - University of Social Welfare and Rehabilitation SciencesHolger Thiele - University of CologneMichael Nothnagel - University of CologneHela Azaiez - University of IowaRichard J Smith - Roy J. and Lucille A. Carver College of MedicineKimia Kahrizi - University of Social Welfare and Rehabilitation SciencesHossein Najmabadi - University of Social Welfare and Rehabilitation Sciences
- Resource Type
- Journal article
- Publication Details
- Clinical genetics, Vol.100(1), pp.59-78
- DOI
- 10.1111/cge.13956
- PMID
- 33713422
- PMCID
- PMC8195868
- NLM abbreviation
- Clin Genet
- ISSN
- 0009-9163
- eISSN
- 1399-0004
- Grant note
- T32 GM007748 / NIGMS NIH HHS R01 DC012049 / NIDCD NIH HHS R01 DC002842 / NIDCD NIH HHS R01 DC017955 / NIDCD NIH HHS
- Language
- English
- Date published
- 07/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984256835402771
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