Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males

Eur J Hum Genet. 2013 Sep;21(9):1012-5. doi: 10.1038/ejhg.2012.290. Epub 2013 Jan 9.

Abstract

The steroidogenic factor 1 (SF1) protein, encoded by the NR5A1 gene, plays a central role in gonadal development and steroidogenesis. Mutations in NR5A1 were first described in patients with primary adrenal insufficiency and 46,XY disorders of sexual development and later also in men with hypospadias, bilateral anorchia and micropenis and women with primary ovarian insufficiency. Recently, heterozygous missense mutations were found in 4% of infertile men with unexplained reduced sperm counts living in France, but all mutation carriers were of non-Caucasian ancestry. Therefore, we performed a comprehensive NR5A1 sequence analysis in 488 well-characterised predominantly Caucasian patients with azoo- or severe oligozoospermia. Two-hundred-thirty-seven men with normal semen parameters were sequenced as controls. In addition to several synonymous variants of unclear pathogenicity, three heterozygous missense mutations predicted to be damaging to SF1 protein function were identified. The andrological phenotype in infertile but otherwise healthy mutation carriers seems variable. In conclusion, mutations altering SF1 protein function and causing spermatogenic failure are also found in men of German origin, but the prevalence seems markedly lower than in other populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • DNA Mutational Analysis
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation, Missense
  • Oligospermia / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Steroidogenic Factor 1 / genetics*

Substances

  • NR5A1 protein, human
  • Steroidogenic Factor 1