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CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis

Nature Genetics volume 19, pages 286–288 (1998)Cite this article

Abstract

The 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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Figure 1: Positional cloning of CLN5.
Figure 2: Mutations in CLN5.
Figure 3: Predicted features of the CLN5 polypeptide.

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Author notes

  1. Eric S. Lander: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA. M.S. and T.K. contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Genetics, University of Helsinki and Department of Human Molecular Genetics, National Public Health Institute, Mannerheimintie 166, Helsinki, 00300, Finland

    Minna Savukoski, Tuomas Klockars, Ville Holmberg & Leena Peltonen

  2. Department of Neurology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland

    Pirkko Santavuori

Authors
  1. Minna Savukoski
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  2. Tuomas Klockars
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  3. Ville Holmberg
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  4. Pirkko Santavuori
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  5. Eric S. Lander
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  6. Leena Peltonen
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Correspondence to Leena Peltonen.

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Savukoski, M., Klockars, T., Holmberg, V. et al. CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis. Nat Genet 19, 286–288 (1998). https://doi.org/10.1038/975

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