title: Diagnostic yield of targeted gene panel sequencing to identify the genetic etiology of disorders of sex development.
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.
authors.affiliation: Department of Pediatrics, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea.
authors.forename: Ja Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eungu
authors.initials: E
authors.lastname: Kang
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Heo
authors.affiliation: Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Gu-Hwan
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Green Cross Genome, Yongin, Republic of Korea.
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Green Cross Genome, Yongin, Republic of Korea.
authors.forename: Eun-Hae
authors.initials: EH
authors.lastname: Cho
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Beom Hee
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Han-Wook
authors.initials: HW
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: jhc@amc.seoul.kr.
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Choi
mesh_terms: D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics; D012734:Disorders of Sex Development / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: Androgen receptor; CYP17A1; Disorders of sex development; Exome sequencing; SRD5A2