Familial autosomal dominant reflex epilepsy triggered by hot water maps to 4q24-q28.
Hot water epilepsy is a reflex or sensory epilepsy in which seizures are triggered by the stimulus of bathing in hot water. Although there is evidence of a genetic basis to its etiology, no gene associated with this disorder has so far been found. In order to identify the genetic locus involved in the pathophysiology of hot water epilepsy, we performed a genome-wide linkage analysis in a four-generation family manifesting the disorder in an autosomal dominant manner. Significant linkage was detected on chromosome 4q24-q28, with the highest two-point LOD score of 3.50 at recombination value (theta) 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 and corresponds to about 24 megabases of DNA. The genes NEUROG2, ANK2, UGT8 and CAMK2D, which are known to be expressed in human brain, are strong positional candidates and we propose to examine these and other genes in the locus to identify the causative gene for this intriguing form of epilepsy.
Ratnapriya
Rinki
R
Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore 560064, India.
Satishchandra
Parthasarthy
P
Dilip
S
S
Gadre
Girish
G
Anand
Anuranjan
A
D001494:Baths / Q000009:adverse effects; D001921:Brain / Q000503:physiopathology; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D004569:Electroencephalography; D020195:Epilepsy, Reflex / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011995:Recombination, Genetic; D012640:Seizures / Q000235:genetics / Q000503:physiopathology
D005819:Genetic Markers