Familial dysautonomia: detection of the IKBKAP IVS20(+6T --> C) and R696P mutations and frequencies among Ashkenazi Jews

Am J Med Genet. 2002 Jul 1;110(3):253-7. doi: 10.1002/ajmg.10450.


Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that occurs almost exclusively in the Ashkenazi Jewish (AJ) population. Mutations in the IkappaB kinase complex-associated protein (IKBKAP) gene cause FD. Two IKBKAP mutations, IVS20(+6T --> C) and R696P, have been identified in FD patients of AJ descent. The splice site mutation IVS20(+6T --> C) is responsible for > 99.5% of known AJ patients with FD, and haplotype analyses were consistent with a common founder. In contrast, the R696P mutation has been identified in only a few AJ patients. To facilitate carrier detection, a single PCR and allele-specific oligonucleotide (ASO) hybridization assay was developed to facilitate the detection of both the IVS20(+6T --> C) and R696P mutations. Screening of 2,518 anonymous AJ individuals from the New York metropolitan area revealed a carrier frequency for IVS20(+6T --> C) of 1 in 32 (3.2%; 95% CI, 2.5-3.9%), similar to the previously estimated carrier frequency (3.3%) based on disease incidence. No carrier was identified for the R696P lesion, indicating that the mutation was rare in this population (< 1 in 2,500). This sensitive and specific assay should facilitate carrier screening for FD mutations in the AJ community, as well as postnatal diagnostic testing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics
  • Carrier Proteins / genetics*
  • DNA / genetics
  • Dysautonomia, Familial / epidemiology
  • Dysautonomia, Familial / genetics*
  • Gene Frequency
  • Genetic Testing
  • Heterozygote
  • Jews / genetics*
  • Mutation
  • Mutation, Missense
  • New York / epidemiology
  • Polymerase Chain Reaction
  • Transcriptional Elongation Factors


  • Carrier Proteins
  • Elp1 protein, human
  • Transcriptional Elongation Factors
  • DNA