An Extended Iranian Family with Autosomal Dominant Non-syndromic Hearing Loss Associated with A Nonsense Mutation in the DIAPH1 Gene

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.

Case report of a novel mutation in the TNC gene in Chinese patients with nonsyndromic hearing loss

“…[27,28] Nowadays, the development of molecular diagnostic technology has greatly reduced the cost of testing, and metagenomic next-generation sequencing has become an effective way of providing comprehensive and efficient diagnosis for hearing loss. [11][12][13][14] To find out the mechanism of hearing loss, timely intervention measures should be taken, such as avoiding taking drugs that can cause deafness, wearing hearing AIDS, and cochlear implants, so that they can leave the silent world as soon as possible and return to normal life.…”

“…[10] In recent times, advancements in molecular diagnostic technology have significantly reduced testing costs, leading to the emergence of metagenomic next-generation sequencing (mNGS) as an effective and comprehensive method for diagnosing NSHL. [11][12][13][14] In this study, we employed mNGS, Sanger sequencing, protein function, and structure analysis, and model prediction to investigate and analyze the molecular biology of a Chinese family affected by nonsyndromic deafness.…”