• PMID: 31219235
• Gene Name: HOXD13
• Condition: Hypospadias
• Association: Associated
• Mutation: c.G32C(p.G11A)
• Population size: 130
• Population details: 137 cases
• Age: 6 months to 18 years old
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Identification of gene variants in 130 Han Chinese patients with hypospadias by targeted next-generation sequencing

Zhang W, Shi J, Zhang C, Jiang X, Wang J, Wang W, Wang D, Ni J, Chen L, Lu W, Xiao Y, Ye W, Dong Z.

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. CI - © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. FAU - Zhang, Wanyu AU - Zhang W AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Shi, Jinxiu AU - Shi J AD - Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai, China. FAU - Zhang, Chenhui AU - Zhang C AD - Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai, China. FAU - Jiang, Xincheng AU - Jiang X AD - Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Junqi AU - Wang J AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Wei AU - Wang W AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Defen AU - Wang D AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ni, Jihong AU - Ni J AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Chen, Lifen AU - Chen L AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Lu, Wenli AU - Lu W AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xiao, Yuan AU - Xiao Y AUID- ORCID: 0000-0002-4927-8199 AD - Department of Paediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ye, Weijing AU - Ye W AD - Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.