HYPEREKPLEXIA-LIKE SYNDROMES WITHOUT MUTATIONS IN THE GLRA1 GENE

Hyperekplexia (MIM: 149400): or startle disease, is an autosomal domin ant neurological disorder characterized by an extreme generalized stif fness immediately after birth, normalizing during the first years of l ife. Other features of this disorder are excessive startle reactions t o unexpected, particularly auditory, stimuli together with a short per iod of generalized stiffness during which voluntary movements are impo ssible. Linkage analysis mapped a gene for this disorder to chromosome 5q33-q35. Subsequently, mutations in the GLRA1 gene encoding the alph a 1-subunit of the glycine receptor proved to be causally related to t he disease. In the present study, mutation analysis of all exon and na nking intron sequences of this gene was performed in sporadic patients and their parents. Moreover, a branch of the original Dutch hyperekpl exia family with a very severely affected individual was screened for an additional mutation in the GLRA1 gene, Except for two polymorphisms , of which one results in an amino acid change, no potentially disease causing mutations were found in the alpha 1-subunit of the glycine re ceptor, Together with haplotype analysis these results exclude a reces sive inheritance or new mutation etiology in these hyperekplexia-like syndromes and emphasize that hyperekplexia-like syndromes can be cause d by other genetic factors. The involvement of other genes encoding su bunits of the functional glycine receptor complex has not been exclude d. (C) 1997 Elsevier Science B.V.