Variants in HEY genes manifest in Ventricular Septal Defects of Congenital Heart Disease

Cardiogenesis starts at around the third week of gestation and require precise gene signalling through various transcription factors. Irregularities in gene signalling lead to various types of Congenital Heart Diseases (CHDs). Since the Ventricular Septal Defects (VSDs) are more frequent in Indians, to unravel the possible genetic players in VSD cases, the whole exome sequence data was generated and analysed. Whole exome sequencing was carried using the Illumina platform and data was analysed with specific softwares. The analysis identified a frameshift deletion (GGCATGT) in Hairy/Enhancer-of-split related with YRPW motif protein 1(HEY1) in transcript NM_001282851 with rs142613628 and in HEY2, a nonsynonymous damaging variant, A370G in the transcript NM_012259 with rs549151246. Further, it was observed that HEY proteins interacted with NOTCH1, GATA4, ZFPM1, NCoR1, MEF2A, JAG1 and HDAC9 proteins which are involved in cardiogenesis. This suggests that variants in HEY genes are involved in manifestation of VSDs and Tetralogy of Fallots (TOFs) indicating their role in heart development. •One frameshift deletion (GGCATGT) in HEY1•One nonsynonymous (A370G) damaging variants in HEY2•HEY proteins interacted with NOTCH1, GATA4, ZFPM1, NCOR1, MEF2A, JAG1 and HDAC9•Variants in HEY genes involved in manifestation of isolated VSDs and VSDs with TOFs