IDENTIFICATION OF 12 NOVEL MUTATIONS IN THE ALPHA-N-ACETYLGLUCOSAMINIDASE GENE IN 14 PATIENTS WITH SANFILIPPO-SYNDROME TYPE-B (MUCOPOLYSACCHARIDOSIS TYPE-IIIB)

Sanfilippo syndrome type B or mucopolysaccharidosis type IIIB (IMPS II IB) is one of a group of lysosomal storage disorders that are characte rised by the inability to breakdown heparan sulphate. In RIPS IIIB, th ere is a deficiency in the enzyme alpha-N-acetylglucosaminidase (NAGLU ) and early clinical symptoms include aggressive behaviour and hyperac tivity followed by progressive mental retardation. The disease is auto somal recessive and the gene for NAGLU, which is situated on chromosom e 17q21, is approximately 8.5 kb in length and contains six exons. Pri mers were designed to amplify the entire coding region and intron/exon boundaries of the NAGLU gene in 10 fragments. The PCR products were a nalysed for sequence changes using SSCP analysis and fluorescent DNA s equencing technology. Sixteen different putative mutations were detect ed in DNA from 14 RIPS IIIB patients, 12 of which have not been found previously. The mutations include four deletions (219-237del19, 334-35 8del25, 1335delC, 2099delA), two insertions (1447-1448insT, 1932-1933i nsGCTAC), two nonsense mutations (R297X, R626X), and eight missense mu tations (F48C, Y140C, R234C, W268R, P521L, R565W, L591P, E705K). In th is study, the Y140C, R297X, and R626X mutations were all found in more than one patient and together accounted for 25% of mutant alleles.