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Identification of 16 sulfamidase gene mutations including the common R74C in patients with mucopolysaccharidosis type IIIA (Sanfilippo A)
Author(s) -
Bunge Susanna,
Ince Hüseyin,
Steglich Cordula,
Kleijer Wim J.,
Beck Michael,
Zaremba Jacek,
van Diggelen Otto P.,
Weber Birgit,
Hopwood John J.,
Gal Andreas
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:6<479::aid-humu10>3.0.co;2-x
Subject(s) - biology , missense mutation , genetics , compound heterozygosity , mutation , allelic heterogeneity , allele , point mutation , mucopolysaccharidosis , heteroduplex , genetic heterogeneity , gene , exon , microbiology and biotechnology , phenotype , biochemistry
Mucopolysaccharidosis type IIIA (MPS IIIA or Sanfilippo A disease) is a storage disorder caused by deficiency of the lysosomal enzyme sulfamidase. Mutation screening, using SSCP/heteroduplex analyses on cDNA and genomic DNA fragments, was performed in a group of 42 European patients. Sixteen of the 17 different gene mutations characterized have not been previously described. The spectrum of gene lesions consists of two 1‐bp deletions (1091delC, 1093delG), an 18‐bp duplication (421ins18), a splice site mutation (IVS2‐2A→G), and 13 different missense point mutations. As in other lysosomal storage disorders, the phenotypic heterogeneity is associated with a considerable genetic heterogeneity. The missense mutation R74C, which alters an evolutionary conserved amino acid in the active site of the enzyme, was found on 56% of alleles of 16 Polish patients, whereas it was less frequent among German patients (21% of disease alleles). R245H, a previously reported common mutation, represents 35% of disease alleles in German patients, but only 3% in Polish patients. As the combined frequency of the common mutations (R74C and R245H) in German and Polish populations exceeds 55%, screening for these two mutations will assist molecular genetic diagnosis of MPS IIIA and allow heterozygote testing in these populations. Hum Mutat 10:479–485, 1997. © 1997 Wiley‐Liss, Inc.