MOLECULAR CHARACTERIZATION OF TYPE-1 GAUCHER DISEASE FAMILIES AND PATIENTS - INTRAFAMILIAL HETEROGENEITY AT THE CLINICAL-LEVEL

Type 1 Gaucher disease families were studied in an attempt to establis h a phenotype/genotype correlation in affected persons and also to ide ntify carriers accurately. In the Portuguese type 1 Gaucher patients, screening for mutations N370S, L444P, R463C, and 1066 + 1 G --> A allo wed the identification of 85% of the alleles among unrelated patients. A subclinical case with genotype N370S/ 1066 + 1 G --> A was identifi ed in one family in which there were three other symptomatic sibs. To our knowledge this is the first subclinical case with a genotype other than N370S/N370S. No genotype-phenotype correlation could be establis hed and considerable clinical heterogeneity was found even among sibs with the same genotype. The data collected on the origins of the Gauch er families indicated two areas in northern Portugal where a higher fr equency of the disease may be expected to exist.