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.

• MeSH
• acetyltransferasy genetika   chemie   metabolismus   MeSH
• buněčné linie MeSH
• exony MeSH
• exprese genu MeSH
• financování organizované MeSH
• klonování DNA MeSH
• komplementární DNA genetika   MeSH
• lidé MeSH
• lidské chromozomy, pár 8 genetika   MeSH
• mapování chromozomů MeSH
• molekulární sekvence - údaje MeSH
• mukopolysacharidóza III enzymologie   genetika   MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• myši MeSH
• polymerázová řetězová reakce MeSH
• rekombinantní fúzní proteiny genetika   metabolismus   MeSH
• rodokmen MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie aminokyselin MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH