title: Rapid Molecular Genetic Diagnosis with Next-Generation Sequencing in 46,XY Disorders of Sex Development Cases: Efficiency and Cost Assessment.
abstract: OBJECTIVE
  The aim of this study was to use targeted next-generation sequencing (TNGS) including all known genes associated with 46,XY disorders of sex development (DSD) for a fast molecular genetic diagnosis.
  
  
  METHODS
  Twenty pediatric patients were recruited, and 56 genes related to 46,XY DSD were sequenced using TNGS. The time elapsed between initial appointment and final diagnosis as well as the mean expenditure was determined.
  
  
  RESULTS
  A total of 9 (45%) mutations in 4 different genes were identified. Mutations in the HSD17B3 gene were observed in 6 (30%) patients. A heterozygous mutation in WT1 gene and a hemizygous mutation in SRY gene were detected in patients with gonadal dysgenesis. One patient had a homozygous mutation in LHCGR gene. Prior to the molecular diagnosis, the mean number of clinical visits, time elapsed until diagnosis, and expenditure were 27.4 ± 14.6 visits, 5.9 ± 4.1 years per patient, and USD 2,142 ± 1,038, respectively. With TNGS, time elapsed until diagnosis was significantly reduced (3 days), and expenditure per patient was only one third of the conventional approach (USD 761).
  
  
  CONCLUSIONS
  TNGS is an efficient, rapid, and cost-effective technique for mutation detection in 46,XY DSD.
authors.affiliation: Department of Pediatric Endocrinology, School of Medicine, Ege University, Izmir, Turkey.
authors.forename: Samim
authors.initials: S
authors.lastname: Özen
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Onay
authors.forename: Tahir
authors.initials: T
authors.lastname: Atik
authors.forename: Aslı Ece
authors.initials: AE
authors.lastname: Solmaz
authors.forename: Ferda
authors.initials: F
authors.lastname: Özkınay
authors.forename: Damla
authors.initials: D
authors.lastname: Gökşen
authors.forename: Şükran
authors.initials: Ş
authors.lastname: Darcan
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D058489:46, XX Disorders of Sex Development / Q000235:genetics*; D000293:Adolescent; D002648:Child; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3