Mucopolysaccharidosis type IIIB (Sanfilippo B): identification of 18 novel α-N-acetylglucosaminidase gene mutations
- Susanna Bungea,
- Astrid Kniggea,
- Cordula Steglicha,
- Wim J Kleijerb,
- Otto P van Diggelenb,
- Michael Beckc,
- Andreas Gala
- aInstitut für Humangenetik, Universitäts-Krankenhaus Eppendorf, Butenfeld 42, 22529 Hamburg, Germany, bDepartment of Clinical Genetics, University Hospital, Erasmus University, Rotterdam, The Netherlands, cUniversitäts-Kinderklinik, Mainz, Germany
- Dr Bunge.
- Received 25 March 1998
- Revised 18 June 1998
Abstract
Mucopolysaccharidosis type IIIB (MPS IIIB or Sanfilippo B disease) is an autosomal recessive storage disorder caused by deficiency of the lysosomal enzyme α-N-acetylglucosaminidase. Mutation screening was performed on a group of 22 patients using a combination of SSCP/heteroduplex analysis of amplified genomic fragments and direct sequencing of cDNA fragments. Twenty-one different mutations were identified, 18 of them novel. Together they account for 82% of the disease alleles. The mutation spectrum consists of two small insertions, two small deletions, three nonsense mutations, and 14 different missense mutations, one of them (M1L) affecting the initiation codon. The vast genetic heterogeneity seen in this disorder is reflected by the fact that only three of the mutations were identified in more than one patient.
