Identification and characterisation of mutations underlying Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB).

Sanfilippo syndrome type B or mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme α-Nacetylglucosaminidase (NAG, EC 3.2.1.50). NAG catalyses the removal of terminal α-N-acetylglucosamine residues from heparan sulphate. In the absence of NAG, partially degraded heparan sulphate accumulates in tissues and is excreted in the urine. Affected subjects show developmental delay, attention deficit disorder, uncontrollable hyperactivity, and aggressive behaviour, followed by progressive dementia with death usually in the late teens. Cloning of the NAG gene and cDNA has enabled studies of the molecular basis of this syndrome. 3 At present, over 50 different mutations underlying MPS IIIB have been identified, including deletions, insertions, point mutations, and splicing site mutations. The extensive allelic heterogeneity reflects the wide spectrum of clinical phenotypes reported in MPS IIIB patients. In this study, the molecular lesions of six unrelated Chinese patients with MPS IIIB were investigated. Five novel and two previously reported mutations were found. We used transient expression studies to examine the effects of the mutations on NAG catalytic activity, mRNA stability, and protein stability.