Gaucher disease: Biochemical and molecular findings in 141 patients diagnosed in Greece.
Por:
Dimitriou E, Moraitou M, Cozar M, Serra-Vinardell J, Vilageliu L, Grinberg-Vaisman DR, Mavridou I and Michelakakis H
Publicada:
1 sep 2020
Ahead of Print:
7 jun 2020
Resumen:
Gaucher disease (GD) is characterized by a marked phenotypic and genetic diversity. It is caused by the functional deficiency of the lysosomal enzyme ß-glucocerebrosidase (GCase), which in most instances results from mutations in the GBA1 gene and over 500 different disease causing mutations have been described. We present the biochemical and molecular findings in 141 GD cases (14 were siblings) with the three types of the disorder diagnosed in Greece over the last 35 years. 111/141 (78%) GD patients were of Greek origin. The remaining patients were Albanian (24/141; 17%), Syrian (2/141; 1.4%), Egyptian (2/141; 1.4%), Italian (1/141; 0.7%) and Polish (1/141; 0.7%). Mutation analysis identified 28 different mutations and 37 different genotypes. Seven of the mutations were not previously reported (T231I, D283N, N462Y, LI75P, F81L, Y135S and T482K). The most frequent mutations were N370S, D409H;H255Q and L444P. Mutation D409H;H255Q was only identified in Greek and Albanian patients. Sixteen mutations, including the novel ones, were identified only in one allele. Although the N370S mutation was identified only in type 1 patients, not all of type 1 patients carried this mutation. Our results highlight the heterogeneity of Gaucher disease and support the Balkan origin of the double mutant allele D409H;H255Q.
Filiaciones:
Dimitriou E:
Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece
Moraitou M:
Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece
Cozar M:
Department de Genètica, Microbiologia i Estadistica, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
Serra-Vinardell J:
Department de Genètica, Microbiologia i Estadistica, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
Vilageliu L:
Department de Genètica, Microbiologia i Estadistica, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
Grinberg-Vaisman DR:
Department de Genètica, Microbiologia i Estadistica, Universitat de Barcelona, CIBERER, IBUB, IRSJD, Barcelona, Spain
Mavridou I:
Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece
Michelakakis H:
Department of Enzymology and Cellular Function, Institute of Child Health, Athens, Greece
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