Molecular characterisation 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 establish a phenotype/genotype correlation in affected persons and also to identify carriers accurately. In the Portuguese type 1 Gaucher patients, screening for mutations N370S, L444P, R463C, and 1066 + 1 G-->A allowed the identification of 85% of the alleles among unrelated patients. A subclinical case with genotype N370S/1066 + 1 G-->A was identified 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 established and considerable clinical heterogeneity was found even among sibs with the same genotype. The data collected on the origins of the Gaucher families indicated two areas in northern Portugal where a higher frequency of the disease may be expected to exist.