A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors.
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.
Brune
W
W
Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
Weber
R G
RG
Saul
B
B
von Knebel Doeberitz
M
M
Grond-Ginsbach
C
C
Kellerman
K
K
Meinck
H M
HM
Becker
C M
CM
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
D018009:Receptors, Glycine