A novel genetic locus for juvenile myoclonic epilepsy at chromosome 5q12–q14

Abstract

Juvenile myoclonic epilepsy is a clinically well-defined, age-related common idiopathic generalized epilepsy syndrome with substantial genetic basis to its etiology. We report identification of a novel epilepsy locus at chromosome 5q12-q14 in a family exhibiting autosomal dominant form of juvenile myoclonic epilepsy from south India. The highest two-point LOD score of 3.3344 was obtained for the microsatellite markers D5S641 and D5S459 at 5q14. Centromeric and telomeric chromosomal boundaries of the locus were defined by D5S624 and D5S428, respectively. The 5q12-q14 locus encompasses about 25 megabases of the genomic region and harbours several candidate genes. Further work involving a detailed mutational analysis of the locus, to isolate the gene responsible for the epilepsy disorder in the family, shall help enhance our understanding of molecular basis of epilepsy disorders.

Interstitial deletion 5q14.3q21.3 with MEF2C haploinsufficiency and mild phenotype: When more is less

“…Febrile seizures confer a 5‐ to 7‐fold increased risk for epilepsy, and one of several loci (FEB4‐MIM60453) was defined by linkage studies of 48 families [Nakayama et al, 2000, 2002]. Nearby is a locus for autosomal dominant juvenile myoclonic epilepsy (EJM4‐MIM611364) linked to region 5q12q14 in a Southern Indian family with teenage onset of myoclonic jerks and generalized epilepsy without febrile seizures [Kapoor et al, 2007]. Differentiation of epilepsy loci is also suggested by the one family among those studied by Nakayama et al [2002] who had both febrile and afebrile seizures due to a nonsense mutation in a G‐protein‐coupled receptor 98 (GPR98) gene at 5q14.3 (89,890,373–90,495,789 bp).…”

A locus for juvenile myoclonic epilepsy maps to 2q33–q36

“…Genetic loci or genes for JME have been mapped at 5q34 (GABRA1, Cossette et al 2002), 6p21.2-p11 (EFHC1, Suzuki et al 2004), 6p21 (Greenberg et al 1988;Durner et al 1991;Sander et al 1997), 15q14 (Elmslie et al 1997), 5q12-q14 (Kapoor et al 2007). Genetic loci at 7q32 and 16p13 have been found in families, where photoparoxysmal response (PPR) occurs along with a prominent myoclonic epilepsy background (Pinto et al 2005), while loci at 6p21 and 13q31 have been linked with PPR with absence seizures and partial epilepsies (Tauer et al 2005).…”

Genetic Generalized Epilepsies

“…A mutation was found in the GABRA1 gene on chromosome 5q34, which encodes for the alpha subunit of the GABA-A receptor, and was inherited in an autosomal dominant fashion. Susceptibility for JME have been reported to exist on the following loci: chromosome 6p12.2 (EFHC1), 6p21, 15q14 (CHRNA7), 3q27.2 (CLCN2), 1p36.33 (GABRD), 5q34 (GABRA1), 2q23.3 (CACNB4) and 5q12-14 (Cossette et al, 2002;Durner et al, 1991;Elmslie et al, 1997;Escayg et al, 2000a;Kapoor et al, 2007;Liu et al, 1995;Saint-Martin et al, 2009;Sander et al, 1995;Weissbecker et al, 1991). An autosomal recessive form has also been reported (Panayiotopoulos and Obeid, 1989).…”