Familial dysautonomia: Detection of the IKBKAP IVS20+6T → C and R696P mutations and frequencies among Ashkenazi Jews

Jianli Dong, Lisa Edelmann, Asghar M. Bajwa, Ruth Kornreich, Robert J. Desnick

Research output: Contribution to journalArticle

48 Scopus citations


Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that occurs almost exclusively in the Ashkenazi Jewish (AJ) population. Mutations in the IκB kinase complex-associated protein (IKB-KAP) 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.

Original languageEnglish (US)
Pages (from-to)253-257
Number of pages5
JournalAmerican Journal of Medical Genetics
Issue number3
StatePublished - Jul 1 2002
Externally publishedYes


  • Allele-specific oligonucleotide hybridization
  • Ashkenazi Jewish population
  • Familial dysautonomia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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