Familial autosomal dominant reflex epilepsy triggered by hot water maps to 4q24-q28
- 230 Downloads
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 (θ) 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.
KeywordsFebrile Seizure Clobazam Audiogenic Seizure Genetic Interval Dravet Syndrome
We thank all the family members for participation in the study. We thank Sharat Chandra and Prakash for critical reading and comments on the manuscript. RR acknowledges receipt of a research fellowship from CSIR, New Delhi. This work was supported by funds from DAE, Mumbai; ICMR, New Delhi and JNCASR, Bangalore.
Conflict of interest statement
All authors report no financial interests or potential conflicts of interests.
- Allen IM (1945) Observations on cases of reflex epilepsy. NZ Med J 44:135–142Google Scholar
- Dravet C, Bureau M, Guerrini R, Giraud N, Roger J (1992) Severe myoclonic epilepsy in infants. In: Roger J, Dravet C, Bureau M, Dreifuss FE, Perret A, Wolf P (eds) Epileptic syndromes in infancy, childhood and adolescence, 2nd edn. John Libbey, London, pp 75–88Google Scholar
- Keipert JA (1969) Epilepsy precipitated by bathing: water-immersion epilepsy. Aust Paediatr J 5:244–247Google Scholar
- Kong A, Gudbjartsson DF, Sainz J, Jonsdottir GM, Gudjonsson SA, Richardsson B, Sigurdardottir S, Barnard J, Hallbeck B, Masson G, Shlien A, Palsson ST, Frigge ML, Thorgeirsson TE, Gulcher JR, Stefansson K (2002) A high-resolution recombination map of the human genome. Nat Genet 31:241–247PubMedGoogle Scholar
- Kurata S (1979) Epilepsy precipitated by bathing: a follow-up study. Brain Dev (Domestic Ed) 11:400–405Google Scholar
- Moran J (1976) So-called water immersion epilepsy. Ir J Med Sci 145:140Google Scholar
- Pinto D, Westland B, de Haan GJ, Rudolf G, da Silva BM, Hirsch E, Lindhout D, Trenite DG, Koeleman BP (2005) Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for linkage on chromosomes 7q32 and 16p13. Hum Mol Genet 14:171–178CrossRefPubMedGoogle Scholar
- Satishchandra P, Ullal GR, Sinha A, Shankar SK (1999) Pathophysiology and genetics of hot-water epilepsy. In: Bercovic S, Genton P, Marescaux C, Picard F (eds) Genetics of focal epilepsies: clinical aspects and molecular biology. John Libbey, London, pp 169–176Google Scholar
- Satishchandra P, Ullal GR, Shankar SK (2004) Trigger mechanisms in hot water epilepsy. In: Wolf P, Inoue Y, Zifkin B (eds) Reflex epilepsies. John Libbey, UK, pp 105–114Google Scholar
- Tauer U, Lorenz S, Lenzen KP, Heils A, Muhle H, Gresh M, Neubauer BA, Waltz S, Rudolf G, Mattheisen M, Strauch K, Nurnberg P, Schmitz B, Stephani U, Sander T (2005) Genetic dissection of photosensitivity and its relation to idiopathic generalized epilepsy. Ann Neurol 57:866–873CrossRefPubMedGoogle Scholar
- Velmurugendran CU (1985) Reflex epilepsy. J Neurol 232(Suppl):212Google Scholar