Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novelalpha-N-acetylglucosaminidase gene mutations

Mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo B disease) is an au to somal recessive storage disorder caused by deficiency of the lysosomal e nzyme alpha-N-acetylglucosaminidase. Mutation screening was performed on a group of 22 patients using a combination of SSCP/heteroduplex analysis of a mplified genomic fragments and direct: sequencing of cDNA fragments. Twenty -one different mutations were identified, 18 of them novel. Together they a ccount for 82% of the disease alleles. The mutation spectrum consists of tw o small insertions, two small deletions, three nonsense mutations, and 14 d ifferent missense mutations, one of them (M1L) affecting the initiation cod on. The vast genetic heterogeneity seen in this disorder is reflected by th e fact that only three of the mutations were identified in more than one pa tient.