Mutational and haplotype analysis of the {alpha}{sub 1} subunit of the glycine receptor in hyperekplexia patients
- Univ. of California, Irivne, CA (United States); and others
Familial hyperekplexia or Startle disease (STHE) is a rare autosomal dominant neurologic disorder manifested by marked muscular hypertonia in infants and exaggerated startle response that persists throughout the lifetime of the patient. This disorder is caused by mutations in the {alpha}{sub 1} subunit of the receptor for the inhibitory neurotransmitter glycine (GLRA1). Previously, we have reported three mutations, two of which change arginine 271 (Arg 271) to uncharged amino acids and a third which changes a tyrosine at amino acid 279 to a cysteine. The most common mutation, detected in three of six original families, is a G to A transition mutation at Arg 271. Four new STHE patients have been screened and were found to have the most common Arg 271 mutation. Three of the new patients have a clear family history while family information on the fourth patient was unavailable. Four possible sporadic cases of STHE have been screened by DGGE in all exons of the GLRA1 gene and no mutations have been detected. These sporadic cases may represent defects from other causes. A new three-allele dinucleotide repeat polymorphism at the GLRA1 locus has been detected. Haplotype analysis of two polymorphisms at the GLRA1 locus and CA-repeat polymorphism, D5S119, suggests that the most common mutation arose at least two and most likely three independent times. Thus, it appears that at least five independent GLRA1 mutation events (two of which are identical) have occurred in ten STHE families. The fact that these mutations affect only two amino acids suggests that the dominant STHE phenotype can only be caused by abnormalities in a highly restricted region of GLRA1.
- OSTI ID:
- 134323
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1056
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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