MUTATION ANALYSIS OF 28 GAUCHER DISEASE PATIENTS - THE AUSTRALASIAN EXPERIENCE

Gaucher disease is the most common lysosomal storage disease. It is an autosomal recessive disorder that results from a deficiency of beta-g lucocerebrosidase. Three clinical phenotypes have been described: non- neuronopathic, acute neuronopathic, and subacute neuronopathic. Genomi c DNA from 28 Australasian patients of diverse ethnic origin with Gauc her disease was screened for 3 common mutations (1226G, 1448C and 84GG ) using the amplification refractory mutation system (ARMS), and one u ncommon mutation (1504T) by restriction enzyme digestion. Thirty-eight of the 56 independent alleles in these patients were characterized, w ith 1448C present in 42% and 1226G in 28% of the alleles. The 1226G mu tation was associated only with the non-neuronopathic phenotype and 7 of the 15 patients who carried the 1448C mutation developed neuronopat hic disease. Three infants who died in the neonatal period following a rapidly progressive neurodegenerative course carried no identifiable mutations. The 84GG mutation was carried by 2 Jewish patients and 1504 T was present in one patient. It is now possible to rapidly identify t he common Gaucher mutations using ARMS and restriction enzyme digestio n, and our findings confirm the heterogeneity of mutations in Gaucher disease. It is also possible to predict in part the phenotypic outcome when screening patients for these mutations. We consider mutation ana lysis to be of most use in prenatal diagnosis and for carrier detectio n within affected families. (C) 1994 Wiley-Liss, Inc.