A novel nonsense mutation in HSD17B3 gene in a Tunisian patient with sexual ambiguity

J Sex Med. 2013 Oct;10(10):2586-9. doi: 10.1111/j.1743-6109.2012.02763.x. Epub 2012 May 17.

Abstract

Introduction: 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).

Aim: 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.

Conclusion: 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.

Keywords: 46,XY Disorders of Sex Development; HSD17B3 Deficiency; HSD17B3 Gene Mutation; Testosterone-Δ4 Androstenedione Ratio.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / blood
  • 17-Hydroxysteroid Dehydrogenases / deficiency*
  • 17-Hydroxysteroid Dehydrogenases / genetics
  • Androstenedione / blood
  • Biomarkers / blood
  • Child, Preschool
  • Codon, Nonsense*
  • DNA Mutational Analysis / methods
  • Disorder of Sex Development, 46,XY / blood
  • Disorder of Sex Development, 46,XY / diagnosis
  • Disorder of Sex Development, 46,XY / enzymology
  • Disorder of Sex Development, 46,XY / genetics*
  • Exons
  • Female
  • Genetic Predisposition to Disease
  • Gynecomastia / blood
  • Gynecomastia / diagnosis
  • Gynecomastia / enzymology
  • Gynecomastia / genetics*
  • Homozygote
  • Humans
  • Male
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Steroid Metabolism, Inborn Errors / blood
  • Steroid Metabolism, Inborn Errors / diagnosis
  • Steroid Metabolism, Inborn Errors / enzymology
  • Steroid Metabolism, Inborn Errors / genetics*
  • Testosterone / blood
  • Tunisia

Substances

  • Biomarkers
  • Codon, Nonsense
  • Testosterone
  • Androstenedione
  • 17-Hydroxysteroid Dehydrogenases
  • 17beta-hydroxysteroid dehydrogenase type 3

Supplementary concepts

  • 17-Hydroxysteroid Dehydrogenase Deficiency