Diagnostic yield of targeted gene panel sequencing to identify the genetic etiology of disorders of sex development. (15th March 2017)

• Record Type: Journal Article
• Authors: Kim, Ja Hye; Kang, Eungu; Heo, Sun Hee; Kim, Gu-Hwan; Jang, Ja-Hyun; Cho, Eun-Hae; Lee, Beom Hee; Yoo, Han-Wook; Choi, Jin-Ho
• Is Part Of: Molecular and cellular endocrinology. Volume 444(2017)
• Page Start: 19
• Page End: 25
• Publication Date: 2017-03-15
• Subjects: Androgen receptor -- CYP17A1 -- Disorders of sex development -- Exome sequencing -- SRD5A2; DSD disorders of sex development -- NGS next-generation sequencing -- VUS variants of uncertain clinical significance; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2017.01.037
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Disorders of sex development (DSD) vary phenotypically and are caused by a number of genetic etiologies. This study investigated the genetic etiology of DSD patients using targeted exome sequencing of 67 known DSD-associated genes in humans. This study included 37 patients with 46, XY DSD and seven patients with 46, XX DSD. We identified known pathogenic mutations or deletion in nine (20.5%) patients in the AR, CYP17A1, SRD5A1, and DMRT1/2 genes. Novel variants were identified in nine patients (20.5%) in the AR, ATRX, CYP17A1, CHD7, MAP3K1, NR5A1, and WWOX genes. Among them, four patients harbored pathogenic or likely pathogenic variants, while the remaining five patients (11.4%) had variants of uncertain significance. We were able to make a genetic diagnosis in 29.5% of patients with pathogenic or likely pathogenic mutations. Targeted exome sequencing is an efficient tool to improve the diagnostic yield of DSD, despite its phenotypic and genetic heterogeneity. Highlights: This study investigated the genetic etiology of DSD using targeted exome sequencing of 67 known DSD-associated genes. We were able to make a genetic diagnosis in 29.5% of patients with pathogenic or likely pathogenic mutations. Targeted exome sequencing is an efficient tool to improve the diagnostic yield of DSD, despite genetic heterogeneity.