Lidnex #1923

Beutler E, Gelbart T, Kuhl W, Zimran A, West C

Mutations in Jewish Patients With Gaucher Disease

Blood

1992; 79(7):1662-1666

Gaucher disease, the most common glycolipid storage disorder, is a panethnic disease with the highest frequency found in the Askenazi Jews. The purpose of this study was to identify the frequency of the different disease producing mutation in order to establish the most reasonable approach to screening.

DNA from 100 unrelated Gaucher disease patients, 97 of whom were Askenazi Jews and 3 half Jews were analyzed for the mutations which cause the disease. Through the use of polymerase chain reaction amplification and oligonucleotide hybridization, the samples were first tested for the mutation at nucleotide (NT) site 1226. The most common mutation comprising 77 percent of the alleles analyzed. If the mutation at NT 1226 was not found, other know mutations were investigated.

Of the 197 mutated alleles all but 2 were identified and the 5 most common mutations made up 97.5 percent of all the mutations responsible for Gaucher disease. These involve the mutations at nucleotide sites 1226, 84, 1448, 1297 and intron 2. Mutations 1226 and 84 made up 90.4 percent of all the Gaucher disease alleles. As previous studies have, this study concluded that the most common genotype was the 1226G/1226G homozygous with the next most common benign the 1226G/84CS heterozygous gene. Persons with the 1226 homozygotes have a later age of onset with a milder disease course than do patients with other mutations.