A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors

Am J Hum Genet. 1996 May;58(5):989-97.


Dominant missense mutations in the human glycine receptor (GlyR) alpha 1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1(null) allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1 spd-ot), the loss of the GlyR alpha 1 subunit is effectively compensated in man.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Child
  • Female
  • Gene Deletion
  • Genes, Recessive
  • Humans
  • Muscle Contraction / genetics
  • Receptors, Glycine / genetics*
  • Stiff-Person Syndrome / genetics*
  • Stiff-Person Syndrome / metabolism
  • Stiff-Person Syndrome / physiopathology


  • Receptors, Glycine