Identification of gene variants in 130 Han Chinese patients with hypospadias by targeted next‐generation sequencing. Issue 8 (20th June 2019)

• Record Type: Journal Article
• Authors: Zhang, Wanyu; Shi, Jinxiu; Zhang, Chenhui; Jiang, Xincheng; Wang, Junqi; Wang, Wei; Wang, Defen; Ni, Jihong; Chen, Lifen; Lu, Wenli; Xiao, Yuan; Ye, Weijing; Dong, Zhiya
• Is Part Of: Molecular genetics & genomic medicine. Volume 7:Issue 8(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-06-20
• Subjects: candidate gene -- hypospadias -- next‐generation sequencing -- pathogenic genes; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.827
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Hypospadias is a common congenital malformation of male external genitalia, which mainly manifests as an abnormal urethral opening on the ventral side of the penis. The etiology and clinical phenotype of hypospadias is highly heterogeneous, and its clinical diagnosis is challenging. Currently, over 70% of patients have an unknown etiology. Here, we performed a targeted analysis of gene mutations in 130 patients with hypospadias of unknown etiology to find the precise genetic cause. Methods: We developed a targeted next‐generation sequencing (NGS) panel, encompassing the exon coding regions of 105 genes involved in external genitalia and urogenital tract development and performed sequencing analysis on 130 children with hypospadias of unknown etiology. Results: In total, 25 patients with hypospadias (19.2%) were found to have 20 mutations among the nine genes involved in external genitalia and urogenital tract development, including 16 reported and four novel mutation sites. Twenty‐two patients (16.9%) had diagnostic variants. Multiple genetic mutations were identified in three of the 25 patients. Hypospadias combined with micropenis was the most common phenotype (68%) in 25 patients. Conclusions: Higher frequency mutations were identified in SRD5A2 (52%) and AR (24%) in our patient cohort. Middle or posterior hypospadias with micropenis may be significant indicators of genetic variations. Polygenic inheritance may be a rare genetic cause of hypospadias. Abstract : In this study, we performed targeted next‐generation sequencing of 105 genes associated with molecular regulation of external genitalia and urogenital tract development in 130 patients with hypospadias of unknown etiology. A total of 25 patients (19.2%) were found to carry genetic variants in one or more of the nine targeted genes. We also found that middle or posterior hypospadias with micropenis may represent significant signs for genetic variations.