Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare aut
osomal recessive disease caused by deficiency of alpha-N-acetylglucosa
minidase, one of the enzymes required for the lysosomal degradation of
heparan sulfate. The gene for this enzyme, NAGLU, recently was isolat
ed, and several mutations were characterized. We have identified, in a
mplified exons from nine fibroblast cell lines derived from Sanfilippo
syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C
, E153K, R203X, 650insC, 901delAA, P358L, AG64V, and L682R. Four of th
ese mutations were found in homozygosity, and only two were seen in mo
re than one cell line. Thus, Sanfilippo syndrome type B shows extensiv
e molecular heterogeneity. Stable transfection of Chinese hamster ovar
y cells, by cDNA mutagenized to correspond to the NAGLU missense mutat
ions, did not yield active enzyme, demonstrating the deleterious natur
e of the mutations. Nine of the 10 amino acid substitutions identified
to date are clustered near the amino or the carboxyl end of alpha-N-a
cetylglucosaminidase, suggesting a role for these regions in the trans
port or function of the enzyme.