TY - JOUR
T1 - Familial dysautonomia
T2 - Detection of the IKBKAP IVS20+6T → C and R696P mutations and frequencies among Ashkenazi Jews
AU - Dong, Jianli
AU - Edelmann, Lisa
AU - Bajwa, Asghar M.
AU - Kornreich, Ruth
AU - Desnick, Robert J.
PY - 2002/7/1
Y1 - 2002/7/1
N2 - 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.
AB - 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.
KW - Allele-specific oligonucleotide hybridization
KW - Ashkenazi Jewish population
KW - Familial dysautonomia
KW - IKBKAP
UR - http://www.scopus.com/inward/record.url?scp=0036644252&partnerID=8YFLogxK
U2 - 10.1002/ajmg.10450
DO - 10.1002/ajmg.10450
M3 - Article
C2 - 12116234
AN - SCOPUS:0036644252
SN - 0148-7299
VL - 110
SP - 253
EP - 257
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 3
ER -