Hyperekplexia-like syndromes without mutations in the GLRA1 gene

• Published in: Clinical neurology and neurosurgery Vol. 99; no. 3; pp. 172 - 178
• Main Authors: Vergouwe, M.N., Tijssen, M.A.J., Shiang, R., van Dijk, J.G., Shahwan, Saad Al, Ophoff, R.A., Frants, R.R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.1997
• Subjects: Adult; Child, Preschool; Female; Genetic Markers; Haplotype analysis; Haplotypes - genetics; Humans; Hyperekplexia-like syndromes; Infant; Male; Muscle Rigidity - genetics; Mutation analysis of the GLRAI gene; Netherlands; Pedigree; Point Mutation - genetics; Polymorphism, Genetic - genetics; Receptors, Glycine - genetics; Reflex, Abnormal - genetics; Reflex, Startle - genetics; Syndrome; Netherlands; Hyperekplexia-like syndromes; Mutation analysis of the GLRAI gene; Haplotype analysis
• ISSN: 0303-8467; 1872-6968
• DOI: 10.1016/S0303-8467(97)00022-X

Hyperekplexia (MIM: 149400), or startle disease, is an autosomal dominant neurological disorder characterized by an extreme generalized stiffness immediately after birth, normalizing during the first years of life. Other features of this disorder are excessive startle reactions to unexpected, particularly auditory, stimuli together with a short period of generalized stiffness during which voluntary movements are impossible. Linkage analysis mapped a gene for this disorder to chromosome 5833-q35 Subsequently, mutations in the GLRAI gene encoding the α1-subunit of the glycine receptor proved to be causally related to the disease. In the present study, mutation analysis of all exon and flanking intron sequences of this gene was performed in sporadic patients and their parents. Moreover, a branch of the original Dutch hyperekplexia family with a very severely affected individual was screened for an additional mutation in the GLRAI gene. Except for two polymorphisms, of which one results in an amino acid change, no potentially disease causing mutations were found in the α I-subunit of the glycine receptor. Together with haplotype analysis these results exclude a recessive inheritance or new mutation etiology in these hyperekplexia-like syndromes and emphasize that hyperekplexia-like syndromes can be caused by other genetic factors. The involvement of other genes encoding subunits of the functional glycine receptor complex has not been excluded.