title: Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy.
abstract: Childhood-onset neuronal ceroid lipofuscinoses (NCL) are a group of autosomal recessive progressive encephalopathies characterized by the accumulation of autofluorescent material in various tissues, notably in neurons. Based on clinical features, the country of origin of patients, and the molecular genetic background 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 CLN8 gene. A variant form of late infantile NCL (vLINCL) present in Turkish patients 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 CLN8 gene region on 8p23 in four out of five Turkish vLINCL families studied. However, no common mutation in CLN8 was found in these families. We have now extended the Turkish vLINCL family panel to 18 families, of which only one is nonconsanguineous. Nine families were excluded from CLN8 by lack of homozygosity. In the remaining families, four CLN8 gene mutations were identified indicating that in a subset of patients with Turkish vLINCL, the disorder is allelic to Northern epilepsy. There is no apparent genotype-phenotype correlation among the Turkish patients with CLN8 mutations, although their phenotype is distinct from that of Finnish Northern epilepsy patients. The molecular genetic background of the Turkish vLINCL families not linked to CLN8 remains to be clarified.
authors.affiliation: Folkhälsan Institute of Genetics and Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Ranta
authors.forename: Meral
authors.initials: M
authors.lastname: Topcu
authors.forename: Saara
authors.initials: S
authors.lastname: Tegelberg
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Tan
authors.forename: Alp
authors.initials: A
authors.lastname: Ustübütün
authors.forename: Isil
authors.initials: I
authors.lastname: Saatci
authors.forename: Andreas
authors.initials: A
authors.lastname: Dufke
authors.forename: Herbert
authors.initials: H
authors.lastname: Enders
authors.forename: Keith
authors.initials: K
authors.lastname: Pohl
authors.forename: Yves
authors.initials: Y
authors.lastname: Alembik
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Mitchell
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
authors.forename: Anna-Elina
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D014421:Turkey
chemical_list: C121767:CLN8 protein, human; D008565:Membrane Proteins