Nature Genetics
19, 286 - 288 (1998)
doi:10.1038/975
CLN5, a novel gene encoding a putative transmembrane protein mutated
in Finnish variant late infantile neuronal ceroid lipofuscinosisMinna Savukoski1, Tuomas Klockars1, Ville Holmberg1, Pirkko Santavuori2, Eric S. Lander3
& Leena Peltonen11
Department of Medical Genetics, University of Helsinki
and Department of Human Molecular Genetics, National Public Health Institute,
Mannerheimintie 166, 00300 Helsinki, Finland. 2
Hospital for Children and Adolescents, Department of
Neurology, University of Helsinki, Helsinki, Finland. 3
Whitehead Institute for Biomedical Research,
Cambridge, Massachusetts, USA.
M.S. and T.K. contributed equally to this work.
Correspondence should be addressed to Leena Peltonen Leena.Peltonen@ktl.fiThe neuronal ceroid lipofuscinoses (NCLs) represent a group of common
recessive inherited neurodegenerative disorders of childhood, with an incidence
of 1:12,500 live births1. They are characterized by accumulation
of autofluorescent lipopigments in various tissues. Several forms of NCLs
have been identified, based on age at onset, progression of disease, neurophysiological
and histopathological findings and separate genetic loci2,
3,
4,
5,
6,
7,
8,
9.
All types of NCL cause progressive visual and mental decline, motor disturbance,
epilepsy and behavioral changes, and lead to premature death. One of the subtypes,
Finnish variant late infantile neuronal ceroid lipofuscinosis (vLINCL; MIM256731)
affects children at 4−7 years of age10,
11. The first
symptom is motor clumsiness, followed by progressive visual failure, mental
and motor deterioration and later by myoclonia and seizures. We have previously
reported linkage for vLINCL on chromosome 13 (ref. 5)
and constructed a long-range physical map over the region12.
Here, we report the positional cloning of a novel gene, CLN5, underlying
this severe neurological disorder. The gene encodes a putative transmembrane
protein which shows no homology to previously reported proteins. Sequence
analysis of DNA samples from patients with three different haplotypes revealed
three mutations; one deletion, one nonsense and one missense mutation, suggesting
that mutations in this gene are responsible for vLINCL.
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