Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state

Journal Article · Sun Dec 01 00:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.23.10544· OSTI ID:5821087

Beutler, E; Gelbart, T; Kuhl, W; Sorge, J; West, C ^[1]

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1. Scripps Research Inst., La Jolla, CA (United States)

Gaucher disease is an autosomal recessive glycolipid storage disease characterized by a deficiency of glucocerebrosidase. The disease is most common in persons of Ashkenazi Jewish ancestry and the most common mutation, accounting for about 75% of the mutant alleles in this population, is known to be an A {yields} G substitution at cDNA nucleotide (nt) 1,226. Screening for this disease has not been possible because nearly 25% of the mutant alleles had not been identified, but linkage analysis led to the suggestion that most of these could be accounted for by a single mutation. The authors now report the discovery of this mutation. The insertion of a single nucleotide, a second guanine at cDNA nt 84 (the 84GG mutation), has been detected in the 5{prime} coding region of the glucocerebrosidase gene. The amount mRNA produced is shown to be normal but since the frameshift produces early termination, no translation product is seen. This finding is consistent with the virtual absence of antigen found in patients carrying this mutation. The 84GG mutation accounts for most of the previously unidentified Gaucher disease mutations in Jewish patients. The common Jewish mutation at nt 1,448 accounted for 95% of all of the Gaucher disease-producing alleles in 71 Jewish patients. This now makes it possible to screen for heterozygotes on a DNA level with a relatively low risk of missing couples at risk for producing infants with Gaucher disease.

• OSTI ID: 5821087
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:23; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GLUCOSIDASE
ENZYME ACTIVITY
HEREDITARY DISEASES
RISK ASSESSMENT
RECOMBINANT DNA
DNA SEQUENCING
ELECTROPHORESIS
ETIOLOGY
MESSENGER-RNA
PATIENTS
RECESSIVE MUTATIONS
SCREENING
DISEASES
DNA
ENZYMES
GLYCOSYL HYDROLASES
HYDROLASES
MUTATIONS
NUCLEIC ACIDS
O-GLYCOSYL HYDROLASES
ORGANIC COMPOUNDS
PROTEINS
RNA
STRUCTURAL CHEMICAL ANALYSIS
550400* - Genetics