MST1R Gene Variants Predispose Individuals to Tetralogy of Fallot.

IF 3.7 Q2 GENETICS & HEREDITY

Phenomics (Cham, Switzerland) Pub Date : 2025-01-21 eCollection Date: 2024-12-01 DOI:10.1007/s43657-024-00175-9

Zhiyu Feng, Xianghui Huang, Yuan Gao, Han Gao, Weilan Na, Chaozhong Tan, Shaojie Min, Yuquan Lu, Quannan Zhuang, Siyi Lin, Xiaojing Ma, Weicheng Chen, Weili Yan, Wei Sheng, Guoying Huang

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Abstract

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 Macrophage stimulating 1 receptor (MST1R) 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 MST1R, c.T2009G: p.V670G, in two offspring with TOF in a single family. Targeted sequencing of the MST1R gene showed enrichment for rare variants in 417 TOF patients compared with East Asians in Genome Aggregation Database Version 2 (gnomADv2_EAS). MST1R-deficient human induced pluripotent stem cells (hiPSCs) maintained normal pluripotency but differentiated into non-functional cardiomyocytes (CMs). Taken together, our findings indicate that MST1R may play a critical role in cardiac differentiation and genetic variations in MST1R may be associated with the pathogenesis of TOF.

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

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Phenomics (Cham, Switzerland)

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