KMT2C Polymorphism in Familial Hypospadias

Abstract

Hypospadias, a common congenital anomaly of male genitalia, shows significant heritability and familial recurrence, particularly in consanguineous families. This study explored the role of KMT2C polymorphisms in a Yemeni family with two affected siblings. Comprehensive analysis identified 475 unique SNPs in KMT2C, with 59 shared between parents, suggesting common ancestry. Key interactions with genes such as MAP3K1, ATRX, and CHD7 implicated in sex differentiation were noted. Novel findings included a deleterious BAHD1 mutation and a de novo rs201834857 variant linked to Kleefstra syndrome 2. The study emphasizes the multifactorial etiology of hypospadias, integrating genetic, epigenetic, and environmental factors, and highlights the need for further research.

Keywords: BAHD1; KMT2C; Genetic architecture; Hypospadias; Lysine methyltransferase 2C; Whole exome sequencing.