Mutational analysis of SRY: nonsense and missense mutations in XY sex reversal

Hum Genet. 1992 Feb;88(4):471-4. doi: 10.1007/BF00215684.


XY females (n = 17) were analysed for mutations in SRY (sex-determining region Y gene), a gene that has recently been equated with the testis determining factor (TDF). SRY sequences were amplified by the polymerase chain reaction (PCR) and analysed by both the single strand conformational polymorphism assay (SSCP) and DNA sequencing. The DNA from two individuals gave altered SSCP patterns; only these two individuals showed any DNA sequence variation. In both cases, a single base change was found, one altering a tryptophan codon to a stop codon, the other causing a glycine to arginine amino acid substitution. These substitutions lie in the high mobility group (HMG)-related box of the SRY protein, a potential DNA-binding domain. The corresponding regions of DNA from the father of one individual and the paternal uncle of the other, were sequenced and found to be normal. Thus, in both cases, sex reversal is associated with de novo mutations in SRY. Combining this data with two previously published reports, a total of 40 XY females have now been analysed for mutations in SRY. The number of de novo mutations in SRY is now doubled to four, adding further strength to the argument that SRY is TDF.

MeSH terms

  • Base Sequence
  • Codon / genetics
  • DNA-Binding Proteins / genetics*
  • Disorders of Sex Development
  • Female
  • Genetic Variation
  • Gonadal Dysgenesis, 46,XY
  • High Mobility Group Proteins / genetics
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Nuclear Proteins*
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic*
  • Restriction Mapping
  • Sex Determination Analysis
  • Sex-Determining Region Y Protein
  • Transcription Factors*
  • Tryptophan
  • X Chromosome*
  • Y Chromosome*


  • Codon
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • SRY protein, human
  • Sex-Determining Region Y Protein
  • Transcription Factors
  • Tryptophan

Associated data

  • GENBANK/S78409
  • GENBANK/S78411
  • GENBANK/S78413
  • GENBANK/S78753
  • GENBANK/S83238
  • GENBANK/S83241
  • GENBANK/S83242
  • GENBANK/S83243
  • GENBANK/S83252
  • GENBANK/S83254