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

Citation

Maran, Sathiya (2020), Mutations in the tail domain of MYH3 contributes to atrial septal defect, Dryad, Dataset, https://doi.org/10.5061/dryad.pvmcvdnh3

Abstract

Atrial septal defect (ASD) is one of the most common congenital heart defects (CHDs) 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=2.36 (1.36-4.11)] 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 these genes can be used as panel for diagnosis of ASD in future.

Methods

This is a genotyping data generated by sequencing patinets with atrial septal defect, using the  Nextera XT DNA Sample Preparation Kit (Illumina, San Diego, CA) according to the manufacturer's protocol. A fragment length of the libraries was ascertained using the High Sensitivity DNA kit (Agilent Technologies,Santa Clara, CA) on the 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA). Normalized libraries were subjected to a 300-cycle 153 sequencing run with MiSeq Reagent
Nano Kit v2 (Illumina, San Diego, CA) on the MiSeq (Illumina, San Diego, CA), were carried out the Genetic Laboratory, faculty of Science, University of Malaya.

Funding

Universiti Sains Malaysia, Award: 1001/PPSP/813066