No evidence for a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q

Juvenile myoclonic epilepsy (JME) is a distinct epileptic syndrome with a c omplex mode of inheritance, Several studies found evidence for a locus invo lved in JME on chromosome 6 near the HLA region. Recently, Elmslie et al, [ 1997] reported evidence of linkage in JME to chromosome 15q14 assuming a re cessive mode of inheritance with 50% penetrance and 65% linked families. Th e area on chromosome 15q14 encompasses the location of the gene for the alp ha-7 subunit of the nicotinic acetylcholine receptor. This could fit the hy pothesis that there are two interacting loci, one on chromosome 6 and on ch romosome 15 or that there is genetic heterogeneity in JME. In an independen t dataset of JME families, we tested for linkage to chromosome 15 but found little evidence for linkage, Moreover, families with more than one family member affected with JME provide a lodscore of 3.4 for the HLA-DR/DQ haplot ype on chromosome 6, The lodscore for these same families on chromosome 15q 14 is <-2 assuming homogeneity and the maximum lodscore is 0.2 assuming alp ha =.25, Only one of these families has a negative lodscore on chromosome 6 and a positive lodscore of 0.5 on chromosome 15q14, Our results indicate t hat this possible gene on chromosome 15 plays at most a minor role in our J ME families. Am, J, Med, Genet, (Neuropsychiatr. Genet.) 96:49-52, 2000, (C ) 2000 Wiley-Liss, Inc.