title: Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis.
abstract: Neuronal ceroid lipofuscinoses (NCLs) comprise a heterogeneous group of metabolic storage diseases that present with the accumulation of autofluorescent lipopigment, neurodegeneration and premature death. Nine genes have been thus far identified as the cause of different types of NCL, with ages at onset ranging from around birth to adult, although the underlying etiology of the disease still remains elusive. We present a family with typical NCL pathology in which we performed exome sequencing and identified a single homozygous mutation in ATP13A2 that fully segregates with disease within the family. Mutations in ATP13A2 are a known cause of Kufor-Rakeb syndrome (KRS), a rare parkinsonian phenotype with juvenile onset. These data show that NCL and KRS may share etiological features and implicate the lysosomal pathway in Parkinson's disease.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Susanne A
authors.initials: SA
authors.lastname: Schneider
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Guerreiro
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000235:genetics*; D010375:Pedigree; D006180:Proton-Translocating ATPases / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C514983:ATP13A2 protein, human; D006180:Proton-Translocating ATPases