Homozygous Ala65Pro Mutation with V89L Polymorphism in SRD5A2 Deficiency

J Clin Res Pediatr Endocrinol. 2016 Jun 5;8(2):218-23. doi: 10.4274/jcrpe.2495. Epub 2016 Jan 12.

Abstract

Objective: Deficiency of steroid 5-alpha reductase type 2 (5αRD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5αRD2 deficiency.

Methods: 5αRD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated.

Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients.

Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5αRD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common.

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / deficiency*
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics*
  • Abnormal Karyotype
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Disorders of Sex Development / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Membrane Proteins / deficiency*
  • Membrane Proteins / genetics*
  • Mutation
  • Polymorphism, Single Nucleotide
  • Turkey
  • Young Adult

Substances

  • Membrane Proteins
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • SRD5A2 protein, human