Search

Idiopathic generalized epilepsy (IGE) comprises a heterogeneous group of disorders, in which a high genetic predisposition and a complex mode of inheritance have been suggested. However, genes, which confer liability to common IGE subtypes including juvenile myoclonic epilepsy (JME) and childhood absence epilepsy (CAE) have not been identified so far. Here, we tested the hypothesis that genetic variation in the human homolog of the ««activity-regulated cytoskeleton-associated gene»» (ARC) contributes to the etiology of common IGE disorders. The gene has recently been mapped to chromosome 8q24.3, a region which spans previously identified major IGE susceptibility loci. A systematic search for mutations was performed in 143 patients with a known family history of IGE. However, no evidence for functional variants was found in theARCcoding sequence. Nevertheless, we detected a novel common C489T single nucleotide polymorphism, which provides a useful marker in genetic linkage and association studies. By performing a population- and family-based study we however failed to show significant association between this novel single nucleotide polymorphism and IGE, a finding, which most likely rules out that genetic variation in or close to the ARCgene confers liability to common IGE subtypes.

The authors report a 73-year-old patient with a natural history of early-onset ALS for 49 years presenting with limb and bulbar amyotrophy and a pyramidal syndrome. Analysis of the locus SPG4 identified a heterozygous duplication mutation (c.304_309dupGCCTCG) within exon 1 of the spastingene. We propose that sequence alterations of spastinmay comprise a genetic risk factor in a greater spectrum of motor neuron disorders including clinical variants of ALS.