Molecular analysis of Gaucher disease in a Vietnamese-Czechoslovak patient with high residual glucocerebrosidase activity.
A Vietnamese-Czechoslovak type 1 Gaucher disease patient with mild hematological complications was found to have approximately 20% of the normal level of fibroblast glucocerebrosidase activity. Using primers that recognize exon 9 sequences of the glucocerebrosidase structural gene absent in the pseudogene, genomic DNA sequences flanking exons 9 and 10 of the glucocerebrosidase structural gene were amplified by the polymerase chain reaction. Allele-specific oligonucleotide hybridization to amplified genomic DNA sequence of exons 9 and 10 showed an A----G transition in exon 9 that resulted in the 370Ser----370Asp substitution in one of the alleles. In the other allele, a T----C transition in exon 10 resulted in the 444Leu----444Pro substitution, creating a NciI cleavage site. The heterozygote status of the patient's parents was confirmed biochemically by the detection of intermediate levels (42-55% of normal) of fibroblast glucocerebrosidase activity. Allele-specific oligonucleotide hybridization to amplified parental genomic DNA showed that the exon 9 mutation was present in the Czechoslovak father, whereas the exon 10 mutation was inherited from the patient's Vietnamese mother. This is the first report of the exon 10 mutation in a person of Vietnamese origin.
Choy
F Y
FY
Department of Pediatrics, Montreal Children's Hospital, Quebec, Canada.
Woo
M
M
Der Kaloustian
V M
VM
D000483:Alleles; D001483:Base Sequence; D002648:Child; D003604:Czechoslovakia / Q000208:ethnology; D005776:Gaucher Disease / Q000235:genetics*; D005796:Genes / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014744:Vietnam / Q000208:ethnology
D005962:Glucosylceramidase