Identification of a common mutation (R245H) in Sanfilippo A patients from The Netherlands.
We have identified a common mutation (R245H) in the sulphamidase gene of Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA, MPS IIIA) patients from The Netherlands. Allele-specific oligonucleotide hybridization was used to determine the incidence of this mutation in 45 unrelated MPS IIIA patients from different regions of The Netherlands. R245H was present in 51 alleles, representing 56.7% of the total allelic population. Of 39 patients, for whom we have uniform clinical details, 13 MPS IIIA patients who were homozygous for this common mutation had a more uniform but severe clinical phenotype than the remaining 21 or 5 patients, containing respectively one or no R245H alleles. The R245H allele had a higher prevalence in western rather than eastern regions of The Netherlands.
Lysosomal Diseases Research Unit, Department of Chemical Pathology, Women's & Children's Hospital, North Adelaide, Australia.
B
B
Weber
J J
JJ
van de Kamp
W J
WJ
Kleijer
X H
XH
Guo
L
L
Blanch
O P
OP
van Diggelen
R
R
Wevers
B J
BJ
Poorthuis
J J
JJ
Hopwood
D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006639:Histidine / Q000235:genetics; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D009426:Netherlands
D006639:Histidine; D001120:Arginine; D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase