Prediction of severity of Gaucher's disease by identification of mutations at DNA level.

The polymerase chain reaction was used to detect four mutations in the DNA of 47 unrelated patients with type I Gaucher's disease (94 Gaucher's disease alleles). Two of the mutations, 1226 and 1448, and a new mutation (XOVR) representing cross-over between the glucocerebrosidase gene and its closely linked pseudogene, were found. There were five genotypes--namely, 1226/1226, 1226/1448, 1226/XOVR, 1226/?, and ?/? (where "?" indicates that none of the four known mutations was present). Severity of the disease was assessed with a scoring index according to age at diagnosis and extent of organ involvement. Mutation 1226 was associated with a mild clinical phenotype, and mutation 1448 with a more severe phenotype. Mutation 1226 is the most common cause of Gaucher's disease in Jewish patients.