title: Type 1 Gaucher disease: molecular, biochemical, and clinical characterization of patients from northern Portugal.
abstract: We report the study of 16 catholic type 1 Gaucher disease patients originating from a well-defined region in the north of Portugal where a relatively high incidence is observed. The patients were screened for mutations: 3060G-->A, 5841A-->G, 5976C-->G, and 6433T-->C, which enabled the identification of 27 of the 32 mutated alleles. Four different genotypes were identified, namely 5841G/6433C (n = 6), 5841G/5841G (n = 5), 5841G/? (n = 4), and 6433C/? (n = 1). All but one of the patients carried at least one 5841G mutated allele, making its frequency 62.5%, which is similar to that described for Ashkenazi Jewish patients. The 5841G homozygotes presented an overall milder clinical profile, whereas no clear genotype/phenotype correlation could be established for heterozygous patients. On the basis of residual glucocerebrosidase activity, no distinction could be made between 5841G homozygotes and 5841G/6433C compound heterozygotes. Patients that had at least one 5841G allele (encoding the Ser 370 mutated enzyme) all presented a cell-type-specific residual glucocerebrosidase activity as well as an increased molecular activity when measured in the presence of the physiological activators.
authors.affiliation: Instituto de Genetica Medica Jacinto de Magalhaes, Porto, Portugal.
authors.forename: O
authors.initials: O
authors.lastname: Amaral
authors.forename: L
authors.initials: L
authors.lastname: Lacerda
authors.forename: R
authors.initials: R
authors.lastname: Santos
authors.forename: R A
authors.initials: RA
authors.lastname: Pinto
authors.forename: H
authors.initials: H
authors.lastname: Aerts
authors.forename: M C
authors.initials: MC
authors.lastname: Sa Miranda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D005962:Glucosylceramidase