title: Mutation analysis and genotype/phenotype relationships of Gaucher disease patients in Spain.
abstract: Mutations in the glucocerebrosidase (GBA) gene cause Gaucher disease (GD). The aim of this study was to characterise the GBA mutations and analyze genotype/phenotype relationships in 193 unrelated patients from the Spanish GD Registry. We have identified 98.7% of the mutated GBA alleles, finding 56 different GBA mutations and 66 genotypes causing GD in Spain: 47 previously described mutations and 9 novel mutations (4 missense R395C, R463H, W312R and V398I, 1 nonsense R359X, 4 frameshift c.708delC, c.1214-1215delGC, c.1439-1445del7 and c.42-65del24). The most prevalent mutations were N370S and L444P, accounting for 68.7% of the mutated alleles. A wide phenotypic difference was observed within each genotypic group, and 9% of diagnosed type 1 patients developed neurological involvement including parkisonism, tremor, hypoacusia and eye movements. All of these findings indicate that there is a significant genotypic heterogeneity that explains the huge phenotypic variation among Spanish GD patients.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad Ciencias, Universidad de Zaragoza, Plaza San Francisco s/n, 50009, Zaragoza, Spain. palfonso@unizar.es.|Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain. palfonso@unizar.es.
authors.forename: Pilar
authors.initials: P
authors.lastname: Alfonso
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad Ciencias, Universidad de Zaragoza, Plaza San Francisco s/n, 50009, Zaragoza, Spain.|Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: Aznarez
authors.affiliation: Miguel Servet University Hospital, Zaragoza, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Giralt
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Celular, Facultad Ciencias, Universidad de Zaragoza, Plaza San Francisco s/n, 50009, Zaragoza, Spain.|Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocovi
authors.affiliation: Institute Aragones of Health Sciences (I+CS), Zaragoza, Spain.|Miguel Servet University Hospital, Zaragoza, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Giraldo
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005776:Gaucher Disease / Q000097:blood / Q000235:genetics*; D017353:Gene Deletion; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D010641:Phenotype; D013030:Spain
chemical_list: D005962:Glucosylceramidase