Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C).

Abstract	Mucopolysaccharidosis IIIC (MPS IIIC), or Sanfilippo C, represents the only MPS disorder in which the responsible gene has not been identified; however, the gene has been localized to the pericentromeric region of chromosome 8. In an ongoing proteomics study of mouse lysosomal membrane proteins, we identified an unknown protein whose human homolog, TMEM76, was encoded by a gene that maps to 8p11.1. A full-length mouse expressed sequence tag was expressed in human MPS IIIC fibroblasts, and its protein product localized to the lysosome and corrected the enzymatic defect. The mouse sequence was used to identify the full-length human homolog (HGSNAT), which encodes a protein with no homology to other proteins of known function but is highly conserved among plants and bacteria. Mutational analyses of two MPS IIIC cell lines identified a splice-junction mutation that accounted for three mutant alleles, and a single base-pair insertion accounted for the fourth.
Authors	Xiaolian Fan, Huiwen Zhang, Sunqu Zhang, Richard D Bagshaw, Michael B Tropak, John W Callahan, Don J Mahuran
Journal	American journal of human genetics (Am J Hum Genet) Vol. 79 Issue 4 Pg. 738-44 (Oct 2006) ISSN: 0002-9297 [Print] United States
PMID	16960811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	3' Untranslated Regions Proteins RNA Splice Sites RNA, Messenger lysosomal proteins Acetyltransferases HGSNAT protein, human
Topics	3' Untranslated Regions Acetyltransferases (chemistry, deficiency, genetics) Amino Acid Sequence Animals Exons Expressed Sequence Tags Fibroblasts Frameshift Mutation Gene Expression Regulation, Enzymologic HeLa Cells Humans Introns Mice Models, Molecular Molecular Sequence Data Mucopolysaccharidosis III (enzymology, genetics) Proteins Proteomics RNA Splice Sites RNA, Messenger Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Transfection

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