Marzieh Mohseni
1 
, Yusuf Mohammadi
1 , Farzane Zare Ashrafi
1, Fatemeh Ghodratpour
1, Khadijeh Jalalvand
1, Sanaz Arzhangi
1, Mojgan Babanejad
1, Mohammad Hossein Azizi
2, Kimia Kahrizi
1, Hossein Najmabadi
1* 1 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
2 Associate Professor of Otolaryngology, Academy of Medical Sciences of IR Iran, Tehran, Iran
Abstract
Genetic analysis of non-syndromic hearing loss (NSHL) has been challenged due to marked clinical and genetic heterogeneity. Today, advanced next-generation sequencing (NGS) technologies, such as exome sequencing (ES), have drastically increased the efficacy of gene identification in heterogeneous Mendelian disorders. Here, we present the utility of ES and re-evaluate the phenotypic data for identifying candidate causal variants for previously unexplained progressive moderate to severe NSHL in an extended Iranian family. Using this method, we identified a known heterozygous nonsense variant in exon 26 of the DIAPH1 gene (MIM: 602121), which led to “Deafness, autosomal dominant 1, with or without thrombocytopenia; DFNA1” (MIM: 124900) in this large family in the absence of GJB2 disease-causing variants and also OtoSCOPE-negative results. To the best of our knowledge, this nonsense variant (NM_001079812.3):c.3610C>T (p.Arg1204Ter) is the first report of the DIAPH1 gene variant for autosomal dominant non-syndromic hearing loss (ADNSHL) in Iran.