this invention relates to methods and compositions useful for detecting mutations which cause familial dysautonomia . familial dysautonomia , an ashkenazi jewish disorder , is the best known and most frequent of a group of congenital sensory neuropathies and is characterized by widespread sensory and variable autonomic dysfunction . previously , we mapped the fd gene , dys , to a 0 . 5 cm region of chromosome 9q31 and showed that the ethnic bias is due to a founder effect , with & gt ; 99 . 5 % of disease alleles sharing a common ancestral haplotype . to investigate the molecular basis of fd , we sequenced the minimal candidate region and cloned and characterized its 5 genes . one of these , ikbkap , harbors two mutations that can cause fd . the major haplotype mutation is located in the donor splice site of intron 20 . this mutation can result in skipping of exon 20 in the mrna from fd patients , although they continue to express varying levels of wild - type message in a tissue - specific manner . rna isolated from patient lymphoblasts is primarily wild - type , whereas only the deleted message is seen in rna isolated from brain . the mutation associated with the minor haplotype in four patients is a missense mutation in exon 19 that is predicted to disrupt a potential phosphorylation site . our findings indicate that almost all cases of fd are caused by an unusual splice defect that displays tissue - specific expression ; and they also provide the basis for rapid carrier screening in the ashkenazi jewish population .