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Mutations in Jewish patients with Gaucher disease
E Beutler, T Gelbart, W Kuhl, A Zimran and C West
Department of Molecular and Experimental Medicine, Scripps Research
Institute, La Jolla, CA 92037.
DNA from 100 unrelated patients, 97 of whom were Jewish and three half-
Jewish, was analyzed for 22 mutations known to cause Gaucher disease. All
but seven of the alleles were identified as having previously described
mutations. Five of the unidentified mutations proved to be a previously
undescribed nucleotide substitution in a splice junction (IVS2+1) that
causes skipping of exon 2. Thus, only 2 of 197 alleles remained
unidentified. Homozygotes for the most common mutation, that a nucleotide
(nt) 1226, manifested, on average, the mildest disease and the latest age
of onset. The mutation at nt 84 and the newly described IVS2+1 mutation,
which do not produce any enzyme, were associated with earlier onset and
more severe disease. Five of the mutations were considered to be "public,"
in the sense that they were found in more than one unrelated individual.
Screening for these five mutations permitted detection of 97.5% of all
Gaucher alleles in this patient population. Because the mutation at nt 1226
is underrepresented in the patient population and because not all
homozygotes come to medical attention, screening the Ashkenazi population
using DNA analysis should detect approximately 99% of all heterozygotes.
Volume 79,
Issue 7,
pp. 1662-1666,
04/01/1992
Copyright © 1992 by The American Society of Hematology
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