title: CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.
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 births. 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 loci. 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 age. 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 region. 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.
authors.affiliation: Department of Medical Genetics, University of Helsinki, National Public Health Institute, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Savukoski
authors.forename: T
authors.initials: T
authors.lastname: Klockars
authors.forename: V
authors.initials: V
authors.lastname: Holmberg
authors.forename: P
authors.initials: P
authors.lastname: Santavuori
authors.forename: E S
authors.initials: ES
authors.lastname: Lander
authors.forename: L
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary; D005091:Exons; D005387:Finland; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics*; D017384:Sequence Deletion; D014018:Tissue Distribution
chemical_list: C113332:CLN5 protein, human; D018076:DNA, Complementary; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins