title: Homozygosity for the double D409H+H255Q allele in type II Gaucher disease.
abstract: Homozygosity for D409H has been associated with a unique type III subtype of the disease with a phenotype dominated by severe cardiovascular involvement, whereas neurological findings, if present, are restricted to oculomotor apraxia and features such as visceromegaly are either minimal or absent. Using PCR amplification followed by restriction enzyme analysis, 3 patients (1 Greek, 2 Albanians) were IDentified with the D409H/D409H genotype. All shared a very severe early-onset neurological phenotype that classified them as type II. Amplification and sequencing of the full coding region of the GBA gene revealed that all three patients were homozygous not only for D409H but also for H255Q. Both mutations were present on the same allele, as shown by analysis of the parental DNA. The double D409H+H255Q allele was found in heterozygosity in Greek, Bulgarian and Argentinian patients but was not IDentified in any Spanish patients carrying the D409H mutation.
authors.affiliation: Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece, inchildh@otenet.gr.
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis
authors.forename: Marina
authors.initials: M
authors.lastname: Moraitou
authors.forename: Evagelia
authors.initials: E
authors.lastname: Dimitriou
authors.forename: Raul
authors.initials: R
authors.lastname: Santamaria
authors.forename: Gessami
authors.initials: G
authors.lastname: Sanchez
authors.forename: Laura
authors.initials: L
authors.lastname: Gort
authors.forename: Amparo
authors.initials: A
authors.lastname: Chabas
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.forename: Maria
authors.initials: M
authors.lastname: Dassopoulou
authors.forename: Spyros
authors.initials: S
authors.lastname: Fotopoulos
authors.forename: Lluisa
authors.initials: L
authors.lastname: Vilageliu
mesh_terms: D000415:Albania; D000483:Alleles; D004262:DNA Restriction Enzymes / Q000494:pharmacology; D005776:Gaucher Disease / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006115:Greece; D006720:Homozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D001617:beta-Glucosidase / Q000235:genetics*
chemical_list: D004262:DNA Restriction Enzymes; D001617:beta-Glucosidase