IDENTIFICATION OF 31 NOVEL MUTATIONS IN THE N-ACETYLGALACTOSAMINE-6-SULFATASE GENE REVEALS EXCESSIVE ALLELIC HETEROGENEITY AMONG PATIENTS WITH MORQUIO-A-SYNDROME

Mutation analysis of the N-acetylgalactosamine-6-sulfate sulfatase gen e was performed in a group of 35 patients with mucopolysaccharidosis t ype IVA from 33 families, mainly of European origin. By nonra dioactiv e SSCP screening, 35 different gene mutations were identified, 31 of t hem novel. Together they account for 88.6% of the disease alleles of t he patients investigated. The vast majority of the gene alterations pr oved to be point mutations, 23 missense, 2 nonsense, and 3 affecting s plicing. Six small deletions (1-27 bp) and one insertion were also cha racterized. In a Polish family, two mildly affected siblings were comp ound heterozygotes for R94G and R259Q. Their mother was homozygous for the atter point mutation, leading to enzyme deficiency and a borderli ne disease phenotype. (C) 1997 Wiley-Liss, Inc.