Kumar Sourabh, Sharma Jyoti, Sardar Rahila, Jain Vishesh, Dhua Anjan Kumar, Yadav Devendra Kumar, Agarwala Sandeep, Shamsi Monis Bilal, Almaramhy Hamdi Hameed, Singh Harpreet, Kumar Neeta, Pandey Himani, Goel Prabudh
Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, 110029, India.
Vgenomics, Noida, India.
Indian J Pediatr. 2025 May;92(5):538-540. doi: 10.1007/s12098-024-05384-8. Epub 2025 Jan 15.
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.
尿道下裂是男性生殖器常见的先天性异常，具有显著的遗传性和家族复发倾向，在近亲家庭中尤为明显。本研究探讨了KMT2C基因多态性在一个有两名患病同胞的也门家庭中的作用。综合分析在KMT2C基因中鉴定出475个独特的单核苷酸多态性（SNP），其中59个在父母之间共享，提示有共同的祖先。注意到与参与性别分化的基因如MAP3K1、ATRX和CHD7之间的关键相互作用。新发现包括一个有害的BAHD1突变和一个与2型克莱夫斯特拉综合征相关的新发rs201834857变异。该研究强调了尿道下裂的多因素病因，整合了遗传、表观遗传和环境因素，并突出了进一步研究的必要性。
