Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees
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RESEARCH ARTICLE
Open Access
Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees Somayeh Khatami1, Masomeh Askari2, Fatemeh Bahreini3, Morteza Hashemzadeh-Chaleshtori4, Saeed Hematian4 and Samira Asgharzade4*
Abstract Background: Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. Methods: This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. Results: The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) diseasecausing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A: p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. Conclusion: In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL. Keywords: MYO15A, Whole exome sequencing, First approach, Consanguineous
Background Hearing impairment is considered as an etiologically heterogeneous sensory deficiency with incidence 1 in 1000 newborns around the world [1]. In this regard, genetic hearing loss (HL) has been divided into syndromic and non-syndromic types. Considering the high rate of consanguineous marriages in the Middle East, autosomal recessive non-syndromic hearing loss (ARNSHL) is reportedly more prevalent western countries [2]. However; due to the wide variety of pathogenic genes associated with nonsyndromic hearing loss (NSHL), including both nuclear and mitochondrial ones, the disease includes diverse patterns of inheritance comprised of autosomal * Correspondence: [email protected] 4 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran Full list of author information is available at the end of the article
dominant, autosomal recessive, mitochondrial, and Xlinked recessive. Disease heterogeneity has been admittedly recognized as the most important challenge in genetic diagnosis of NSHL. Diagnostic approaches which have been relied on conventional methods based on genetic testing of the most common genes, often fail to determine the exact genetic cause of the disease in many countries including Iran [3]. In heterogeneous populations like Iran, the distribution of mutations in the gap junction beta-2 protein, also known as connexin 26, (i.e. GJB2) gene as a
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