Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy

Childhood-onset neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive progressive encephalopathies characterized by the accumulation of autofluorescentmaterial in various tissues, notably in neurons. Based on clinical features, the country of origin of patients, and the molecular geneticbackground of the disorder, at least seven different forms are thought to exist. Northern epilepsy is a novel form of NCL so far described only in Finland, where all patients are homozygous for a missense mutation in the CLN8gene. A variant form of late infantile NCL (vLINCL) present in Turkishpatients has been considered a distinct clinical and genetic entity among the NCL, the underlying gene (CLN7) being unknown. Recently, we reported homozygosity over the Northern epilepsy CLN8gene region on 8p23 in four out of five TurkishvLINCL families studied. However, no common mutation in CLN8was found in these families. We have now extended the TurkishvLINCL family panel to 18 families, of which only one is nonconsanguineous. Nine families were excluded from CLN8by lack of homozygosity. In the remaining families, four CLN8gene mutations were identified indicating that in a subset of patients with TurkishvLINCL, the disorder is allelic to Northern epilepsy. There is no apparent genotype-phenotype correlation among the Turkishpatients with CLN8mutations, although their phenotype is distinct from that of Finnish Northern epilepsy patients. The molecular geneticbackground of the TurkishvLINCL families not linked to CLN8remains to be clarified. HumMutat 23:300–305, 2004 © 2004 Wiley-Liss, Inc.