title: A novel nonsense mutation in HSD17B3 gene in a Tunisian patient with sexual ambiguity.
abstract: BACKGROUND
  17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) isoenzyme is present almost exclusively in the testes and converts delta 4 androstenedione to testosterone. Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD).
  
  
  OBJECTIVE
  This study aimed to present the clinical and biochemical features of a Tunisian patient who presented a sexual ambiguity orienting to HSD17B3 deficiency and to search for a mutation in the HSD17B3 gene by DNA sequencing.
  
  
  METHODS
  Polymerase chain reaction (PCR) amplification and subsequent sequencing of all the coding exons of HSD17B3 gene were performed on genomic DNA from the patient, her family, and 50 controls.
  
  
  RESULTS
  Genetic mutation analysis of the HSD17B3 gene revealed the presence of a novel homozygous nonsense mutation in the exon 9 (c.618 C>A) leading to the substitution p.C206X. The mutation p.C206X in the coding exons supports the hypothesis of HSD17B3 deficiency in our patient.
  
  
  CONCLUSIONS
  The patient described in this study represented a new case of a rare form of 46,XY DSD, associated to a novel gene mutation of HSD17B3 gene. The screening of this mutation is useful for confirming the diagnosis of HSD17B3 deficiency and for prenatal diagnosis.
authors.affiliation: Human Molecular Genetic Laboratory, Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia Department of Medical Genetics, Hedi Chaker Hospital, Sfax, Tunisia Department of Endocrinology, Hedi Chaker Hospital, Sfax, Tunisia Department of Pediatrics, Hedi Chaker Hospital, Sfax, Tunisia.
authors.forename: Bochra
authors.initials: B
authors.lastname: Ben Rhouma
authors.forename: Neila
authors.initials: N
authors.lastname: Belguith
authors.forename: Mouna Feki
authors.initials: MF
authors.lastname: Mnif
authors.forename: Thouraya
authors.initials: T
authors.lastname: Kamoun
authors.forename: Nadia
authors.initials: N
authors.lastname: Charfi
authors.forename: Mahdi
authors.initials: M
authors.lastname: Kamoun
authors.forename: Fatma
authors.initials: F
authors.lastname: Abdelhedi
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.forename: Hassen
authors.initials: H
authors.lastname: Kamoun
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abid
authors.forename: Faiza
authors.initials: F
authors.lastname: Fakhfakh
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D000735:Androstenedione / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods; D058490:Disorder of Sex Development, 46,XY / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006177:Gynecomastia / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D043202:Steroid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D013739:Testosterone / Q000097:blood; D014416:Tunisia
chemical_list: D015415:Biomarkers; D018389:Codon, Nonsense; D013739:Testosterone; D000735:Androstenedione; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3