title: Glucocerebrosidase gene mutations in black South Africans with Gaucher disease.
abstract: Gaucher disease (GD) is caused by mutations in the glucocerebrocidase gene (GBA) and presents with variable severity. Type 1 is characterized by the lack of neurological symptoms in childhood, whereas types 2 and 3 are early onset neuronopathic forms and result in premature death. Only type 1 GD has been reported in black South Africans and the cases are clinically severe. In this study both GBA mutations were identified in 18/19 black GD patients. Two mutations accounted for 2/3 of all observed disease causing alleles: p.T36del (c.222-224delTAC) (17/38 alleles) and RecNcil (8/38 alleles). Three novel variants were identified and assessed as being likely pathogenic mutations: c.413delC, W357C and D405V. Haplotype analysis supported a single origin for the p.T36del mutation in black South Africans on a haplotype background that is rare in the present population. We hypothesise that the p.T36del results in intracellular mislocalisation of the protein, but confirmation of the altered function of this allele awaits functional studies. A diagnostic test for GD has been implemented for black South Africans.
authors.affiliation: Division of Human Genetics, National Health Laboratory Service and School of Pathology, University of the Witwatersrand, Johannesburg, Johannesburg, South Africa. silke.arndt@nhls.ac.za
authors.forename: Silke
authors.initials: S
authors.lastname: Arndt
authors.forename: Rene
authors.initials: R
authors.lastname: Heitner
authors.forename: Anthony
authors.initials: A
authors.lastname: Lane
authors.forename: Michèle
authors.initials: M
authors.lastname: Ramsay
mesh_terms: D044383:Black People / Q000235:genetics*; D005776:Gaucher Disease / Q000208:ethnology* / Q000235:genetics*; D005962:Glucosylceramidase / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D009154:Mutation; D013019:South Africa / Q000453:epidemiology
chemical_list: D005962:Glucosylceramidase