Exome sequencing utility in defining the genetic landscape of hearing loss and novel‐gene discovery in Iran. Issue 1 (24th March 2021)

• Record Type: Journal Article
• Authors: Mohseni, Marzieh; Babanejad, Mojgan; Booth, Kevin T.; Jamali, Payman; Jalalvand, Khadijeh; Davarnia, Behzad; Ardalani, Fariba; Khoshaeen, Atefeh; Arzhangi, Sanaz; Ghodratpour, Fatemeh; Beheshtian, Maryam; Jahanshad, Faezeh; Otukesh, Hasan; Bahrami, Fatemeh; Seifati, Seyed Morteza; Bazazzadegan, Niloofar; Habibi, Farkhonde; Behravan, Hanieh; Mirzaei, Sepide; Keshavarzi, Fatemeh; Nikzat, Nooshin; Mehrjoo, Zohreh; Thiele, Holger; Nothnagel, Michael; Azaiez, Hela; Smith, Richard J.; Kahrizi, Kimia; Najmabadi, Hossein
• Is Part Of: Clinical genetics. Volume 100:Issue 1(2021)
• Page Start: 59
• Page End: 78
• Publication Date: 2021-03-24
• Subjects: consanguinity -- exome sequencing -- gene discovery -- hearing loss -- Iran; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13956
• Languages: English
• ISSNs: 0009-9163

Abstract

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. Abstract : In this study, we performed exome sequencing on 71 families from a large cohort of Iranian hereditary hearing loss patients. For 70 out of 71 the GJB2 sequencing and targeted OtoSCOPE panel analysis were negative. We identified likely causal variants in 11 known deafness and eight novel candidate genes. Overall, we could resolve the underlying genetic cause for 28.1% of the previously unresolved families.