Mutation of the parkinsonism gene ATP13A2 causes neuronal ceroid-lipofuscinosis

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 o...

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Bibliographic Details
Published in:Human molecular genetics 2012-06, Vol.21 (12), p.2646-2650
Main Authors: BRAS, Jose, VERLOES, Alain, SCHNEIDER, Susanne A, MOLE, Sara E, GUERREIRO, Rita J
Format: Article
Language:English
Subjects:
Adult
Age
Amino Acid Sequence
Basal ganglia
Base Sequence
Biological and medical sciences
Central nervous system diseases
Data processing
DNA Mutational Analysis
Errors of metabolism
Etiology
Exome - genetics
Family Health
Female
Fundamental and applied biological sciences. Psychology
Genetic Predisposition to Disease - genetics
Genetics of eukaryotes. Biological and molecular evolution
Homozygote
Humans
Lipids (lysosomal enzyme disorders, storage diseases)
Male
Medical sciences
Metabolic diseases
Molecular and cellular biology
Molecular Sequence Data
Movement disorders
Mutation
Neurodegeneration
Neurodegenerative diseases
Neuronal ceroid lipofuscinosis
Neuronal Ceroid-Lipofuscinoses - genetics
Neuronal Ceroid-Lipofuscinoses - pathology
Parkinson's disease
Parkinsonian Disorders - genetics
Pedigree
Proton-Translocating ATPases - genetics
Sequence Homology, Amino Acid
storage diseases
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Summary: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.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/dds089