Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin.
Neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative childhood-onset disorders characterized by autosomal recessive inheritance, epileptic seizures, progressive psychomotor deterioration, visual failure, and premature death. At least seven subtypes of childhood-onset NCLs have been identified of which the late-infantile-onset forms (LINCLs) are genetically the most heterogeneous with four underlying genes identified. A variant form of LINCL (vLINCL) present in Turkish patients has been considered a distinct clinical and genetic entity (CLN7). However, we recently showed that mutations in the CLN8 gene account for a subset of Turkish vLINCL. Toward identifying the CLN7 gene we here screened the known NCL loci for homozygosity in nine Turkish vLINCL families. These loci were excluded in seven families that are likely to represent the 'true' Turkish vLINCL. In two families, we identified two novel homozygous mutations in the CLN6 gene: an intronic base substitution (c.542+5G>T) affecting the splicing of the transcript and a nonsense mutation (c.663C>G) creating a stop codon at tyrosine 221. These data indicate that CLN6 mutations, in addition to those of CLN8, should be considered a diagnostic alternative in Turkish vLINCL patients. The genetic background of the 'true' Turkish vLINCL, CLN7, remains to be defined.
Siintola
E
E
Folkhälsan Institute of Genetics, Department of Medical Genetics and Neuroscience Center, Biomedicum Helsinki, University of Helsinki, Finland.
Topcu
M
M
Kohlschütter
A
A
Salonen
T
T
Joensuu
T
T
Anttonen
A-K
AK
Lehesjoki
A-E
AE
D017668:Age of Onset; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000208:ethnology* / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D014421:Turkey / Q000208:ethnology
C447500:CLN6 protein, human; D008565:Membrane Proteins