Sanfilippo syndrome type B or mucopolysaccharidosis type IIIB (MPS IIIB) is one of a group of lysosomal storage disorders that are characterised by the inability to breakdown heparan sulphate.In MPS IIIB, there is a deficiency in the enzyme [small alpha, Greek]-N-acetylglucosaminidase (NAGLU) and early clinical symptoms include aggressive behaviour and hyperactivity followed by progressive mental retardation. The disease is autosomal recessive and the gene for NAGLU, which is situated on chromosome 17q21, is approximately 8.5 kb in length and contains six exons. Primers were designed to amplify the entire coding region and intron/exon boundaries of the NAGLU gene in 10 fragments. The PCR products were analysed for sequence changes using SSCP analysis and fluorescent DNA sequencing technology. Sixteen different putative mutations were detected in DNA from 14 MPS IIIB patients, 12 of which have not been found previously. The mutations include four deletions (219-237del19, 334-358del25, 1335delC, 2099delA), two insertions (1447-1448insT, 1932-1933insGCTAC), two nonsense mutations (R297X, R626X), and eight missense mutations (F48C, Y140C, R234C, W268R, P521L, R565W, L591P, E705K). In this study, the Y140C, R297X, and R626X mutations were all found in more than one patient and together accounted for 25% of mutant alleles.
(J Med Genet 1998;35:910-914)