Background: Hyperekplexia, also known as startle disease or stiff-person syndrome, is a neurological condition characterized by neonatal hypertonia and a highly exaggerated startle reflex. Genetic studies have linked mutations in the gene encoding glycine receptor α1 (GLRA1) with hereditary hyperekplexia.
Methods: We analyzed four Turkish families with a history of hyperekplexia. Genomic DNA was obtained from members of these families, and the entire coding sequence of GLRA1 was amplified by PCR followed by the sequencing of PCR products. DNA sequences were analyzed by direct observation using an electropherogram and compared with a published reference sequence.
Results: We identified three novel mutations in GLRA1. These included a large deletion removing the first 7 of 9 exons, a single-base deletion in exon 8 that results in protein truncation immediately after the deletion, and a missense mutation in exon 7 causing a tryptophan-to-cysteine change in the first transmembrane domain (M1). These mutant alleles have some distinct features as compared to previously identified GLRA1 mutations. Our data provides further evidence for mutational heterogeneity in GLRA1. The new mutant alleles reported here should advance our understanding of the etiology of hyperekplexia.
Clonazepam Piracetam Glycine Receptor Turkish Family Startle Disease
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We thank Y. Ilkin for translating the Patient Consent Form into Turkish, and K. Petras for DNA isolation. We also thank the hyperekplexia patients and their families for participating in this study.
This study was supported by the Howard Hughes Medical Institute (to Drs Gilbert and Lahn), and the Searle Scholarship and Burroughs Wellcome Career Award (to Dr Lahn).
The authors have no potential conflicts of interest directly relevant to the content of this study.
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