title: Molecular characterization of type 3 (neuronopathic) Gaucher disease in Thai patients.
abstract: Gaucher disease is an autosomal recessive lysosomal storage disorder due to deficiency of the lysosomal enzyme glucocerebrosidase. Three clinical phenotypes, type 1, nonneuronopathic; and types 2 and 3, acute and subacute neuronopathic are recognized. The incidence of Gaucher disease in the Thai population is unknown, but likely under-diagnosed. We performed molecular analysis in four patients, from three sibships, with type 3 Gaucher disease. Four mutant glucocerebrosidase (GBA) alleles were identified including two novel splice site mutations, IVS6-1G>C and IVS9-3C>G; both are predicted to result in truncated protein products, p.F255fsX256, and p.K464fsX487 and p.S463fsX480, respectively. One patient, homozygous for the L444P point mutation, had a "Norbottnian-like" phenotype, with more severe visceral involvement, kyphosis, barreled chest, and no neurological involvement other than supranuclear gaze palsy. These molecular studies of neuronopathic Gaucher disease will provide additional genotype-phenotype correlation particularly in non-Caucasian population.
authors: Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand.
authors: P
authors: P
authors: Suwannarat
authors: S
authors: S
authors: Keeratichamroen
authors: D
authors: D
authors: Wattanasirichaigoon
authors: L
authors: L
authors: Ngiwsara
authors: J R K
authors: JR
authors: Cairns
authors: J
authors: J
authors: Svasti
authors: A
authors: A
authors: Visudtibhan
authors: S
authors: S
authors: Pangkanon
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D005260:Female; D005776:Gaucher Disease / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D005962:Glucosylceramidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D013785:Thailand
chemical_list: D005962:Glucosylceramidase