Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene

Nat Genet. 1995 Feb;9(2):160-4. doi: 10.1038/ng0295-160.


Leydig cell hypoplasia is a rare autosomal recessive condition that interferes with normal development of male external genitalia in 46,XY individuals. We have studied two Leydig cell hypoplasia patients (siblings born to consanguineous parents), and found them to be homozygous for a missense mutation (Ala593Pro) in the sixth transmembrane domain of the luteinizing hormone (LH) receptor gene. In vitro expression studies showed that this mutated receptor binds human choriogonadotropin with a normal KD, but the ligand binding does not result in increased production of cAMP. We conclude that a homozygous LH receptor gene mutation underlies the syndrome of autosomal recessive congenital Leydig cell hypoplasia in this family. These results have implications for the understanding of the development of the male genitalia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Congenital Abnormalities / etiology
  • Consanguinity
  • Disorders of Sex Development / etiology*
  • Disorders of Sex Development / genetics*
  • Female
  • Homozygote
  • Humans
  • Leydig Cells / pathology*
  • Male
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Receptors, LH / genetics*
  • Signal Transduction / genetics


  • Receptors, LH