Splice junction mutation in some Ashkenazi Jews with Tay-Sachs disease: Evidence against a single defect within this ethnic group

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.11.3955· OSTI ID:5412155

Myerowitz, R ^[1]

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1. National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA)

Tay-Sachs disease is an inherited disorder in which the {alpha} chain of the lysosomal enzyme {beta}-N-acetylhexosaminidase A bears the mutation. Ashkenazi Jews are found to be carriers for a severe type of Tay-Sachs disease, the classic form, 10 times more frequently than the general population. Ashkenazi Jewish patients with classic Tay-Sachs disease have appeared to be clinically and biochemically identical, and the usual assumption has been that they harbor the same {alpha}-chain mutation. The author has isolated the {alpha}-chain gene from an Ashkenazi Jewish patient, GM2968, with classic Tay-Sachs disease and compared its nucleotide sequences with that of the normal {alpha}-chain gene in the promoter region, exon and splice junction regions, and polyadenylylation signal area. Only one difference was observed between these sequences. The alteration is presumed to be functionally significant and to result in aberrant mRNA splicing. Utilizing the polymerase chain reaction to amplify the region encompassing the mutation, the author developed an assay to screen patients and heterozygote carriers for this mutation. Surprisingly, in each of two Ashkenazi patients, only one {alpha}-chain allele harbored the splice junction mutation. Only one parent of each of these patients was positive for the defect. Another Ashkenazi patient did not bear this mutation at all nor did either of the subject's parents. The data are consistent with the presence of more than one mutation underlying the classic form of Tay-Sachs disease in the Ashkenazi Jewish population.

• OSTI ID: 5412155
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:11; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMINE OXIDASES
MUTATIONS
GENES
DNA SEQUENCING
HEREDITARY DISEASES
ETIOLOGY
OXIDOREDUCTASES
DNA
FIBROBLASTS
HUMAN POPULATIONS
LYSOSOMES
PATIENTS
PHOSPHORUS 32
PLASMIDS
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BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
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NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
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ORGANOIDS
PHOSPHORUS ISOTOPES
POPULATIONS
RADIOISOTOPES
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
550401* - Genetics- Tracer Techniques