The molecular basis of Sanfilippo syndrome type B.
The Sanfilippo syndrome type B is a lysosomal storage disorder caused by deficiency of alpha-N-acetylglucosaminidase; it is characterized by profound mental deterioration in childhood and death in the second decade. For understanding the molecular genetics of the disease and for future development of DNA-based therapy, we have cloned the cDNA and gene encoding alpha-N-acetylglucosaminidase. Cloning started with purification of the bovine enzyme and use of a conserved oligonucleotide sequence to probe a human cDNA library. The cDNA sequence was found to encode a protein of 743 amino acids, with a 20- to 23-aa signal peptide immediately preceding the amino terminus of the tissue enzyme and with six potential N-glycosylation sites. The 8.5-kb gene (NAGLU), interrupted by 5 introns, was localized to the 5'-flanking sequence of a known gene, EDH17B, on chromosome 17q21. Five mutations were identified in cells of patients with Sanfilippo syndrome type B: 503del10, R297X, R626X, R643H, and R674H. The occurrence of a frameshift and a nonsense mutation in homozygous form confirms the identity of the NAGLU gene.
Zhao
H G
HG
Department of Biological Chemistry, Brain Research Institute and Molecular Biology Institute, University of California at Los Angeles, 90095-1737, USA.
Li
H H
HH
Bach
G
G
Schmidtchen
A
A
Neufeld
E F
EF
D000118:Acetylglucosaminidase / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D009084:Mucopolysaccharidosis III / Q000235:genetics* / Q000473:pathology; D009154:Mutation
D018076:DNA, Complementary; C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase