title: Prediction of severity of Gaucher's disease by identification of mutations at DNA level.
abstract: The polymerase chain reaction was used to detect four mutations in the DNA of 47 unrelated patients with type I Gaucher's disease (94 Gaucher's disease alleles). Two of the mutations, 1226 and 1448, and a new mutation (XOVR) representing cross-over between the glucocerebrosidase gene and its closely linked pseudogene, were found. There were five genotypes--namely, 1226/1226, 1226/1448, 1226/XOVR, 1226/?, and ?/? (where "?" indicates that none of the four known mutations was present). Severity of the disease was assessed with a scoring index according to age at diagnosis and extent of organ involvement. Mutation 1226 was associated with a mild clinical phenotype, and mutation 1448 with a more severe phenotype. Mutation 1226 is the most common cause of Gaucher's disease in Jewish patients.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California.
authors.forename: A
authors.initials: A
authors.lastname: Zimran
authors.forename: J
authors.initials: J
authors.lastname: Sorge
authors.forename: E
authors.initials: E
authors.lastname: Gross
authors.forename: M
authors.initials: M
authors.lastname: Kubitz
authors.forename: C
authors.initials: C
authors.lastname: West
authors.forename: E
authors.initials: E
authors.lastname: Beutler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D005069:Evaluation Studies as Topic; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005784:Gene Amplification; D005838:Genotype; D005959:Glucosidases / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D012720:Severity of Illness Index
chemical_list: D015345:Oligonucleotide Probes; D004247:DNA; D005959:Glucosidases; D005962:Glucosylceramidase