UNLABELLED

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart malformation. While a few susceptibility genes for TOF have been identified, research on the genetic basis of TOF is limited. The () gene encodes the macrophage-stimulating protein receptor with tyrosine phosphatase activity that is involved in immune defense. In this study, we performed whole-exome sequencing (WES) on 10 TOF families and 50 sporadic TOF patients and identified a recessive homozygous missense mutation in , c.T2009G: p.V670G, in two offspring with TOF in a single family. Targeted sequencing of the gene showed enrichment for rare variants in 417 TOF patients compared with East Asians in Genome Aggregation Database Version 2 (gnomADv2_EAS). -deficient human induced pluripotent stem cells (hiPSCs) maintained normal pluripotency but differentiated into non-functional cardiomyocytes (CMs). Taken together, our findings indicate that may play a critical role in cardiac differentiation and genetic variations in may be associated with the pathogenesis of TOF.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s43657-024-00175-9.