title: Prevalence of nine mutations among Jewish and non-Jewish Gaucher disease patients.
abstract: The frequency of nine different mutated alleles known to occur in the glucocerebrosidase gene was determined in 247 Gaucher patients, of whom 176 were of Jewish extraction, 2 were Jewish with one converted parent, and 69 were of non-Jewish origin. DNA was prepared from peripheral blood, active glucocerebrosidase sequences were amplified by using the PCR technique, and the mutations were identified by using the allele-specific oligonucleotide hybridization method. The N37OS mutation appeared in 69.77% of the mutated alleles in Jewish patients and in 22.86% of the mutated alleles in non-Jews. The 84GG mutation, which has not been found so far among non-Jewish patients, existed in 10.17% of the disease alleles among Jewish patients. The IVS + 1 mutation constituted 2.26% of the disease alleles among Jewish patients and 1.43% among the non-Jewish patients. RecTL, a complex allele containing four single-base-pair changes, occurred in 2.26% of the alleles in Jewish patients and was found in two (1.43%) of the patients of non-Jewish extraction. Another complex allele, designated "RecNciI" and containing three single-point mutations, appeared in 7.8% of alleles of non-Jewish patients and in only two (0.56%) of the Jewish families. The prevalence of the L444P mutation among non-Jewish Gaucher patients was 31.43%, while its prevalence among Jewish patients was only 4.24%. The prevalence of two other point mutations--D409H and R463C--was 5.00% and 3.57%, respectively, among non-Jewish patients and was not found among the Jewish Gaucher patient population. The prevalence of the R496H mutation, found so far only among Jewish patients, was 1.13%. The results presented demonstrate that seven mutations identify 90.40% of the mutations among Jewish patients and that these seven mutations allow diagnosis of only 73.52% of the non-Jewish patients. Identification of additional mutant alleles will enhance the accuracy of carrier detection.
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
authors.forename: G
authors.initials: G
authors.lastname: Tzuri
authors.forename: N
authors.initials: N
authors.lastname: Eyal
authors.forename: A
authors.initials: A
authors.lastname: Berebi
authors.forename: E H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: R O
authors.initials: RO
authors.lastname: Brady
authors.forename: N W
authors.initials: NW
authors.lastname: Barton
authors.forename: A
authors.initials: A
authors.lastname: Abrahamov
authors.forename: A
authors.initials: A
authors.lastname: Zimran
mesh_terms: D001483:Base Sequence; D004247:DNA; D005776:Gaucher Disease / Q000235:genetics*; D005784:Gene Amplification; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides; D015995:Prevalence
chemical_list: D009838:Oligodeoxyribonucleotides; D004247:DNA; D005962:Glucosylceramidase