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. Hum Mutat 23:300–305, 2004 © 2004 Wiley‐Liss, Inc.

Phenotypic characterization of a mouse model of juvenile neuronal ceroid lipofuscinosis

“…Mutations in the CLN8 gene in humans are responsible for a form of NCL with similarities to JNCL (Ranta et al, 2004). In a previous study we found that intravitreal implantation of neuralized embryonic stem cells from genetically normal mice into mice with a mutation in the Cln8 gene resulted in a significant retardation in the mutation-related loss of photoreceptor cells from the retina (Meyer et al, 2006).…”

btn1, theSchizosaccharomyces pombehomologue of the human Batten disease geneCLN3, regulates vacuole homeostasis

“…The NCLs are inherited in an autosomal recessive manner and six human NCL genes have now been identified (International Batten Disease Consortium, 1995;Gao et al, 2002;Ranta et al, 1999;Savukoski et al, 1998;Sleat et al, 1997;Vesa et al, 1995;Vines et al, 1999;Wheeler et al, 2002). Despite a common cellular phenotype of disturbed lysosomal function, not all of the proteins causing NCL are located in this organelle (Heine et al, 2004;Isosomppi et al, 2002;Järvelä et al, 1999;Järvelä et al, 1998;Lonka et al, 2000;Lonka et al, 2004;Mole et al, 2004;Ranta et al, 2004).…”

Palmitoyl-Protein Thioesterase 1 Deficiency in Drosophila melanogaster Causes Accumulation of Abnormal Storage Material and Reduced Life Span

“…The CLN4 and CLN7 genes associated with adult NCL and Turkish vLINCL, respectively, have not been identified. It has been demonstrated recently, however, that a subset of Turkish vLINCL cases are actually allelic variants of EPMR, while the genetic causes of the remaining cases of Turkish vLINCL remain unknown (Ranta et al 2004). Recently, a novel form of NCL was characterized that has been classified as CLN9 (Schulz et al 2004).…”