Ethnicity can predict GLRA1 genotypes in hyperekplexia

J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):341-3. doi: 10.1136/jnnp-2014-307903. Epub 2014 Jun 26.

Abstract

Objectives: Hyperekplexia is predominantly caused by mutations in the α-1 subunit of the inhibitory glycine receptor (GLRA1). Three quarters of cases show autosomal-recessive inheritance.

Methods: We carefully ascertained reports of ethnicity from our hyperekplexia research cohort. These were compared with all published cases of hyperekplexia with an identified genetic cause. Ethnicities were subgrouped as Caucasian, Asian, Arabic, Turkish, Jewish or Afro-American.

Results: We report the ethnicity of 90 cases: 56 cases from our service augmented by 34 cases from the literature. Homozygous deletions of exons 1 to 7 are predominantly seen in people with Turkish backgrounds (n=16/17, p<0.001). In contrast, the dominant point mutation R271 is seen in people of Asian, Caucasian and African-American heritage (n=19) but not in people with Arab or Turkish ethnicities (p<0.001).

Conclusions: Self-declared ethnicity can predict gene-screening outcomes. Cultural practices influence the inheritance patterns and a Caucasian founder is postulated for R271 mutations.

Keywords: Genetics; Movement Disorders; Neurogenetics; Paediatric Neurology.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosome Deletion
  • Cohort Studies
  • Cross-Cultural Comparison
  • DNA Mutational Analysis
  • Ethnicity / genetics*
  • Exons / genetics
  • Gene Frequency / genetics
  • Genes, Dominant / genetics
  • Genes, Recessive / genetics
  • Genetic Carrier Screening
  • Genotype*
  • Homozygote
  • Humans
  • Point Mutation / genetics
  • Receptors, Glycine / genetics*
  • Stiff-Person Syndrome / ethnology*
  • Stiff-Person Syndrome / genetics*

Substances

  • GLRA1 protein, human
  • Receptors, Glycine