Novel CLN8 mutations confirm the clinical and ethnic diversity of late infantile neuronal ceroid lipofuscinosis

Reinhardt K, Grapp M, Schlachter K, Brück W, Gärtner J, Steinfeld R. Novel CLN8 mutations confirm the clinical and ethnic diversity of late infantile neuronal ceroid lipofuscinosis. The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited lysosomal storage diseases and the prototype of chi...

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Published in:Clinical genetics 2010-01, Vol.77 (1), p.79-85
Main Authors: Reinhardt, K, Grapp, M, Schlachter, K, Brück, W, Gärtner, J, Steinfeld, R
Format: Article
Language:English
Subjects:
Adolescent
Child
CLN8
Female
Genetic disorders
Genotype & phenotype
Germany
Humans
LINCL
Male
Membrane Proteins - genetics
Mutation
NCL
neurodegeneration
Neurological disorders
Neurology
Neuronal Ceroid-Lipofuscinoses - ethnology
Neuronal Ceroid-Lipofuscinoses - genetics
Neuronal Ceroid-Lipofuscinoses - pathology
Pakistan
Sequence Deletion
Turkey
v-LINCL
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Summary:Reinhardt K, Grapp M, Schlachter K, Brück W, Gärtner J, Steinfeld R. Novel CLN8 mutations confirm the clinical and ethnic diversity of late infantile neuronal ceroid lipofuscinosis. The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited lysosomal storage diseases and the prototype of childhood onset neurodegenerative disorders. To date, 10 NCL entities (CLN1–CLN10) are known and characterized by accumulation of autofluorescent storage material, age of onset and clinical symptoms. CLN8 was first identified as the causative gene for a late‐onset form with progressive epilepsy and mental retardation in Finnish patients. In addition, CLN8 phenotypes were described in Turkish, Israeli and Italian patients with a more rapid progression of visual loss, epilepsy, ataxia and mental decline. Here, we report the first mutations in German (c.611G>T) and Pakistani (c.709G>A) patients. Our findings confirm previous assumptions that the CLN8 variant can occur in many ethnic groups. So far, large CLN gene deletions are only known for the CLN3 gene. Here, we also describe a novel, large CLN8 gene deletion c.544‐2566_590del2613 in a Turkish family with a slightly more severe phenotype. Our data indicate that patients with clinical signs of late infantile NCL and characteristic ultrastructural inclusions should also be screened for CLN8 mutations independent of their ethnic origin.
ISSN:0009-9163
1399-0004
DOI:10.1111/j.1399-0004.2009.01285.x