title: Hereditary hyperekplexia caused by novel mutations of GLRA1 in Turkish families.
abstract: 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 alpha1 (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.
authors.affiliation: Department of Human Genetics, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois 60637, USA. sgilbert@bsd.uchicago.edu
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Gilbert
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozdag
authors.forename: Umit H
authors.initials: UH
authors.lastname: Ulas
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lahn
mesh_terms: D000483:Alleles; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010375:Pedigree; D018009:Receptors, Glycine / Q000235:genetics*; D016750:Stiff-Person Syndrome / Q000208:ethnology / Q000235:genetics*; D014421:Turkey
chemical_list: C000657604:GLRA1 protein, human; D018009:Receptors, Glycine