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Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome)
- Source :
- American Journal of Human Genetics, 79, 807-19, American Journal of Human Genetics, 79, 5, pp. 807-19, American journal of human genetics, 79(5), 807-819. Cell Press
- Publication Year :
- 2006
-
Abstract
- Contains fulltext : 50018.pdf (Publisher’s version ) (Closed access) Mucopolysaccharidosis IIIC (MPS IIIC, or Sanfilippo C syndrome) is a lysosomal storage disorder caused by the inherited deficiency of the lysosomal membrane enzyme acetyl-coenzyme A: alpha -glucosaminide N-acetyltransferase (N-acetyltransferase), which leads to impaired degradation of heparan sulfate. We report the narrowing of the candidate region to a 2.6-cM interval between D8S1051 and D8S1831 and the identification of the transmembrane protein 76 gene (TMEM76), which encodes a 73-kDa protein with predicted multiple transmembrane domains and glycosylation sites, as the gene that causes MPS IIIC when it is mutated. Four nonsense mutations, 3 frameshift mutations due to deletions or a duplication, 6 splice-site mutations, and 14 missense mutations were identified among 30 probands with MPS IIIC. Functional expression of human TMEM76 and the mouse ortholog demonstrates that it is the gene that encodes the lysosomal N-acetyltransferase and suggests that this enzyme belongs to a new structural class of proteins that transport the activated acetyl residues across the cell membrane.
- Subjects :
- Male
DNA, Complementary
Energy and redox metabolism [NCMLS 4]
Recombinant Fusion Proteins
Mucopolysaccharidosis
DNA Mutational Analysis
Molecular Sequence Data
Nonsense mutation
Gene Expression
Neuroinformatics [DCN 3]
Biology
Transfection
medicine.disease_cause
Polymerase Chain Reaction
Article
Cell Line
Frameshift mutation
Mice
Mucopolysaccharidosis III
Acetyltransferases
Perception and Action [DCN 1]
medicine
Genetics
Animals
Humans
Genetics(clinical)
Amino Acid Sequence
Cloning, Molecular
Genetics (clinical)
Mutation
Base Sequence
Sequence Homology, Amino Acid
Mucopolysaccharidosis Type IIIC
Chromosome Mapping
Exons
Glycostation disorders [IGMD 4]
medicine.disease
Molecular biology
Neuromuscular development and genetic disorders [UMCN 3.1]
Transmembrane protein
Pedigree
Transmembrane domain
Genetic defects of metabolism [UMCN 5.1]
Female
Chromosomes, Human, Pair 8
Subjects
Details
- ISSN :
- 00029297
- Database :
- OpenAIRE
- Journal :
- American Journal of Human Genetics, 79, 807-19, American Journal of Human Genetics, 79, 5, pp. 807-19, American journal of human genetics, 79(5), 807-819. Cell Press
- Accession number :
- edsair.doi.dedup.....0a88bac8f29014d6ae438bd00477c836