Identification of a key recombinant narrows the CADASIL gene region to 8 cM and argues against allelism of CADASIL and familial hemiplegic migraine.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CA-DASIL) is a nonarteriosclerotic, nonamyloid angiopathy characterized by recurrent subcortical ischemic strokes starting in midadulthood and frequently leading to pseudobulbar palsy and dementia. The disease locus has recently been mapped to chromosome 19q12. We have identified a chromosomal crossover in a clinically affected family member, which refines the localization of the CADASIL disease locus. Multipoint linkage analysis established the best estimate for the gene locus within an 8-cM interval bracketed by D19S226 and D19S222. This estimate strongly argues against allelism of CADASIL and familial hemiplegic migraine.