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. 1996 May;58(5):989–997.

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

W Brune 1, R G Weber 1, B Saul 1, M von Knebel Doeberitz 1, C Grond-Ginsbach 1, K Kellerman 1, H M Meinck 1, C M Becker 1
PMCID: PMC1914607  PMID: 8651283

Abstract

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.

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Selected References

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