Mutations in the tail domain of MYH3 contributes to atrial septal defect

Sathiya Maran, Robson Ee, Siti Aisyah Faten, Choi Sy Bing, Kooi Yeong Khaw, Swee Hua Erin Lim, Kok Song Lai, Wan Pauzi Wan Ibrahim, Mohd Rizal Mohd Zain, Kok Gan Chan, Siew Hua Gan, Huay Lin Tan

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    Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36–3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p. Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future.

    Original languageEnglish
    Article numbere0230982
    Number of pages17
    JournalPLoS ONE
    Issue number4
    Publication statusPublished - 21 Apr 2020

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