True hermaphroditism in an XY individual due to a familial point mutation of the SRY gene

J Pediatr Endocrinol Metab. Apr-May 2003;16(4):575-80. doi: 10.1515/jpem.2003.16.4.575.


A number of genes are known to control the development of the testis but the transcription factor SRY encoded on the Y-chromosome is considered to play the major role in initiating the first step in determining testicular differentiation. Mutations in this gene usually result in gonadal dysgenesis, but it is interesting to note that at least three of these mutations have been found to be familial. Furthermore, fewer than 10% of true hermaphrodites carry an XY karyotype, and so far only two patients have been documented to carry a mutation in the SRY gene. We have identified a familial mutation in the SRY gene involving a previously described locus. The index patient was born with severely ambiguous genitalia and on histological examination the gonads revealed true hermaphroditism, containing ovarian as well as testicular tissue. The father, his three brothers, and his first-born son carry the identical mutation. The severely feminized XY individual was diagnosed shortly after birth, gonadectomized and raised as female. SRY was determined by PCR and subsequently sequenced using cycle sequencing. A previously published point mutation was identified at nucleotide position 680 resulting in a non-conservative exchange of the amino acid iso-leucine at position 90 into methionine. This position represents a mutational 'hot spot', which seems to retain a certain amount of protein activity, enabling normal male development in some individuals. The patient is the third one reported in whom a mutation in the SRY gene results in ovarian-like development. Since ovarian development in XY individuals is extremely rare, its mechanism is of great interest. Further studies in this family might allow the identification of factors initiating and stimulating ovarian development. How far these infantile ovaries would have developed normally, however, is merely speculative.

MeSH terms

  • Chromosomes, Human, X
  • Chromosomes, Human, Y
  • Disorders of Sex Development / genetics*
  • Disorders of Sex Development / pathology
  • Family Health
  • Female
  • Genes, sry / genetics*
  • Genitalia / abnormalities*
  • Humans
  • Male
  • Ovary / abnormalities
  • Ovary / pathology
  • Pedigree
  • Point Mutation*
  • Testis / abnormalities
  • Testis / pathology