학술논문

The molecular basis of Sanfilippo syndrome type
Document Type
Academic Journal
Source
Proceedings of the National Academy of Sciences of the United States. June 11, 1996, Vol. 93 Issue 12, p6101, 5 p.
Subject
Mucopolysaccharidosis -- Genetic aspects
Antisense DNA -- Research
Cloning -- Research
Science and technology
Language
ISSN
0027-8424
Abstract
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[prime]-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.