Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 26 3 2023 03 01 An Extended Iranian Family with Autosomal Dominant Non-syndromic Hearing Loss Associated with A Nonsense Mutation in the DIAPH1 Gene 176 180 10.34172/aim.2023.27 EN Marzieh Mohseni https://orcid.org/0000-0003-1200-4044 Yusuf Mohammadi https://orcid.org/0000-0003-0177-369X Farzane Zare Ashrafi Fatemeh Ghodratpour Khadijeh Jalalvand Sanaz Arzhangi Mojgan Babanejad Mohammad Hossein Azizi Kimia Kahrizi Hossein Najmabadi https://orcid.org/0000-0002-6084-7778 Journal Article 10.34172/aim.2023.27 2022 11 14 2023 02 19 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.