Abstracts

Rationale: Hot Water Epilepsy (HWE) a form of reflex or sensory epilepsy wherein seizures are precipitated by an unusual stimulus, the contact of hot water over the head. It is frequently reported from South India. It has complex biological mechanisms that remain largely uncertain. Possible interactions between Genetics and Environmental factors have been hypothesized. We have undertaken a human genetic approach using a whole genome-based analysis to search for genetic loci predisposing to hot water epilepsy. Methods: Whole genome-wide two-point linkage analysis followed by manual haplotype analysis of a multi-generation family, Family-150 and 227 has been carried out. The family had more than 10 affected members and 14 unaffected members available for the study. We typed over 400 microsatellite markers and carried out parametric linkage analysis using an autosomal dominant mode of inheritance. Results: First Locus: Genome wide linkage analysis of the first large family provided evidence of linkage for D105412 to chromosome 10q 21. Analysis of five additional smaller HWE families for same marker on chromosome 10, further strengthened the evidence of linkage to the same chromosomal region with three out of five families showing concordance for the disease haplotype and providing two point LOD score of 4.86 at 60 % penetrance for D105412.The centromere proximal and distal boundaries of the critical genetic interval of about 15Mb at 10q 21.3 - 22.3. Second Locus : A linkage analysis in a four-generation family manifesting the disorder in an autosomal dominant way demonstrated significant linkage with markers on chromosome 4q24-q28, with the highest two-point LOD score of 3.50 at recombination value (?) of 0 for the marker D4S402. Centromere-proximal and centromere-distal boundaries of this locus were defined by the markers D4S1572 and D4S2277, respectively. The critical genetic interval spans 22.5 cM . Conclusions: On the basis of this analysis, we conclude that hot water epilepsy is a genetic disorder. Two definite loci over the chromosome 10 and 4 have been identified for the first time in the literature. We are exploring these regions for the causative gene. Preliminary results will be presented.