Identification of novel SRY mutations and SF1 (NR5A1) changes in patients with pure gonadal dysgenesis and 46,XY karyotype

Mol Hum Reprod. 2011 Jun;17(6):372-8. doi: 10.1093/molehr/gar002. Epub 2011 Jan 17.


Primary amenorrhea due to 46,XY disorders of sexual development (DSD) is complex with the involvement of several genes. Karyotyping of such patients is important as they may develop dysgerminoma and molecular analysis is important to identify the underlying mechanism and explore the cascade of events occurring during sexual development. The present study was undertaken for the genetic analysis in seven patients from five families presenting with primary amenorrhea and diagnosed with pure gonadal dysgenesis. Karyotyping was done and the patients were screened for underlying changes in SRY, desert hedgehog (DHH), DAX1 (NR0B1) and SF1 (NR5A1) genes, mutations in which are implicated in DSD. All the patients had 46,XY karyotype and two novel SRY mutations were found. In Family 1 (Patient S1.1) a missense mutation c.294G>A was seen, which results in a stop codon at the corresponding amino acid (Trp98X) and in Family 2 (Patients S2.1, S2.2 and S2.3), a missense mutation c.334G>A (Glu112Leu) was identified in all affected sisters. Both mutations were seen to occur in the conserved high mobility group box of SRY gene. One heterozygous change c.427G>A resulting in Glu143Lys in DHH gene in one patient and two heterozygous changes in the intronic region of SF1 (NR5A1) gene (c.244+80G>A+ c.1068-20C>T) in another patient were noted. One individual did not show changes in any of the genes analyzed. These results reiterate the importance of SRY and others, such as SF1 (NR5A1) and DHH, that are involved in the cascade of events leading to sex determination and also their role in sex reversal.

MeSH terms

  • Amenorrhea / genetics
  • Amenorrhea / physiopathology
  • DAX-1 Orphan Nuclear Receptor / blood
  • DAX-1 Orphan Nuclear Receptor / genetics*
  • DNA-Binding Proteins / blood
  • DNA-Binding Proteins / genetics*
  • Female
  • Gonadal Dysgenesis, 46,XY* / blood
  • Gonadal Dysgenesis, 46,XY* / genetics
  • Gonadal Dysgenesis, 46,XY* / pathology
  • Hedgehog Proteins / blood
  • Hedgehog Proteins / genetics*
  • Heterozygote
  • Humans
  • Introns
  • Karyotyping
  • Mutation, Missense
  • Pedigree
  • RNA Splicing Factors
  • SOXB1 Transcription Factors / blood
  • SOXB1 Transcription Factors / genetics*
  • Sex Determination Processes / genetics*
  • Sexual Development / genetics
  • Siblings
  • Transcription Factors / blood
  • Transcription Factors / genetics*


  • DAX-1 Orphan Nuclear Receptor
  • DHH protein, human
  • DNA-Binding Proteins
  • Hedgehog Proteins
  • NR0B1 protein, human
  • RNA Splicing Factors
  • SF1 protein, human
  • SOX1 protein, human
  • SOXB1 Transcription Factors
  • Transcription Factors