A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy

Am J Hum Genet. 2000 Nov;67(5):1302-5. doi: 10.1016/S0002-9297(07)62958-9. Epub 2000 Oct 2.


We describe a patient with 46,XY partial gonadal dysgenesis (PGD) who presented with polyneuropathy. Sural nerve pathology revealed peculiar findings characterized by extensive minifascicular formation within the endoneurium and with a decreased density of myelinated fibers. We found, in the patient, a homozygous missense mutation (ATG-->ACG) at the initiating codon in exon 1 of the desert hedgehog (DHH) gene, which predicts a failure of translation of the gene. The same heterozygous mutation was found in the patient's father. This is the first report of a human DHH gene mutation, and the findings demonstrate that mutation of the DHH gene may cause 46, XY PGD associated with minifascicular neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Chromosome Aberrations / genetics*
  • Codon, Initiator / genetics
  • DNA Mutational Analysis
  • Disorders of Sex Development
  • Exons / genetics
  • Female
  • Gonadal Dysgenesis / complications*
  • Gonadal Dysgenesis / genetics*
  • Gonadal Dysgenesis / pathology
  • Hedgehog Proteins
  • Humans
  • Male
  • Mice
  • Mutation, Missense / genetics*
  • Nerve Fibers, Myelinated / pathology
  • Polyneuropathies / complications*
  • Polyneuropathies / genetics*
  • Polyneuropathies / pathology
  • Protein Biosynthesis
  • Proteins / genetics*
  • Syndrome
  • Trans-Activators*
  • X Chromosome / genetics
  • Y Chromosome / genetics


  • Codon, Initiator
  • Hedgehog Proteins
  • Proteins
  • Trans-Activators