title: A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors.
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.
authors.affiliation: Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Brune
authors.forename: R G
authors.initials: RG
authors.lastname: Weber
authors.forename: B
authors.initials: B
authors.lastname: Saul
authors.forename: M
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: C
authors.initials: C
authors.lastname: Grond-Ginsbach
authors.forename: K
authors.initials: K
authors.lastname: Kellerman
authors.forename: H M
authors.initials: HM
authors.lastname: Meinck
authors.forename: C M
authors.initials: CM
authors.lastname: Becker
mesh_terms: D000483:Alleles; D002648:Child; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive; D006801:Humans; D009119:Muscle Contraction / Q000235:genetics; D018009:Receptors, Glycine / Q000235:genetics*; D016750:Stiff-Person Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D018009:Receptors, Glycine