DOI: 10.1126/science.2522679. The Mutations in Ashkenazi Jews with Adult G <sub>M2</sub> Gangliosidosis, the Adult Form of Tay-Sachs Disease

The Mutations in Ashkenazi Jews with Adult G M2 Gangliosidosis, the Adult Form of Tay-Sachs Disease

10.1126/science.2522679

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The adult form of Tay-Sachs disease, adult G M2 gangliosidosis, is an autosomal recessive disorder that results from mutations in the α chain of β-hexosaminidase A. This disorder, like infantile Tay-Sachs disease, is more frequent in the Ashkenazi Jewish population. A point mutation in the α-chain gene was identified that results in the substitution of Gly 269 with Ser in eight Ashkenazi adult G M2 gangliosidosis patients from five different families. This amino acid substitution was shown to depress drastically the catalytic activity of the α chain after expression in COS-1 cells. All of these patients proved to be compound heterozygotes of the allele with the Gly to Ser change and one of the two Ashkenazi infantile Tay-Sachs alleles. These findings will aid in the diagnosis and understanding of β-hexosaminidase A deficiency disorders.

Bibliography

Navon, R., & Proia, R. L. (1989). The Mutations in Ashkenazi Jews with Adult G M2 Gangliosidosis, the Adult Form of Tay-Sachs Disease. Science, 243(4897), 1471â1474.

Authors 2

Ruth Navon (first)
Richard L. Proia (additional)

References 45 Referenced 105

10.1038/333085a0
AVIV, H, PURIFICATION OF BIOLOGICALLY-ACTIVE GLOBIN MESSENGER-RNA BY CHROMATOGRAPHY ON OLIGOTHYMIDYLIC-ACID-CELLULOSE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 69: 1408 (1972). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1972)
BAYLERAN, J, SYNTHESIS OF 4-METHYLUMBELLIFERYL-BETA-D-N-ACETYLGLUCOSAMINE-6-SULFATE AND ITS USE IN CLASSIFICATION OF GM2 GANGLIOSIDOSIS GENOTYPES, CLINICA CHIMICA ACTA 143: 73 (1984). (10.1016/0009-8981(84)90215-8) / CLINICA CHIMICA ACTA (1984)
10.1021/bi00591a005
CONZELMANN, E, GANGLIOSIDE-GM2 N-ACETYL-BETA-D-GALACTOSAMINIDASE ACTIVITY IN CULTURED FIBROBLASTS OF LATE-INFANTILE AND ADULT GM2-GANGLIOSIDOSIS PATIENTS AND OF HEALTHY PROBANDS WITH LOW HEXOSAMINIDASE LEVEL, AMERICAN JOURNAL OF HUMAN GENETICS 35: 900 (1983). / AMERICAN JOURNAL OF HUMAN GENETICS (1983)
DALE, AJD, FAMILIAL HEXOSAMINIDASE-A DEFICIENCY WITH KUGELBERG-WELANDER PHENOTYPE AND MENTAL CHANGE, ANNALS OF NEUROLOGY 14: 109 (1983). / ANNALS OF NEUROLOGY (1983)
d'Azzo, A., Journal of Biological Chemistry 259: 11070 (1984). (10.1016/S0021-9258(18)90623-X) / Journal of Biological Chemistry (1984)
10.1016/0003-2697(83)90418-9
FRISCH, A, HEXOSAMINIDASE A DEFICIENT ADULTS - PRESENCE OF ALPHA-CHAIN PRECURSOR IN CULTURED SKIN FIBROBLASTS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 119: 101 (1984). (10.1016/0006-291X(84)91624-3) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1984)
GLUZMAN, Y, SV40-TRANSFORMED SIMIAN CELLS SUPPORT THE REPLICATION OF EARLY SV40 MUTANTS, CELL 23: 175 (1981). (10.1016/0092-8674(81)90282-8) / CELL (1981)
GRABOWSKI, G.A., CHRONIC BETA-HEXOSAMINIDASE-A DEFICIENCY - CLINICAL AND BIOCHEMICAL-STUDIES OF A NEW NEUROMUSCULAR DISEASE, PEDIATRIC RESEARCH 14: 632 (1980). / PEDIATRIC RESEARCH (1980)
GRAHAM, T.R., MOLECULAR-CLONING OF THE CDNA WHICH ENCODES BETA-N-ACETYLHEXOSAMINIDASE-A FROM DICTYOSTELIUM-DISCOIDEUM - COMPLETE AMINO-ACID SEQUENCE AND HOMOLOGY WITH THE HUMAN ENZYME, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 16823 (1988). (10.1016/S0021-9258(18)37465-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1988)
GREENBERG, D.A., ESTIMATION OF THE FREQUENCY OF HEXOSAMINIDASE-A VARIANT ALLELES IN THE AMERICAN JEWISH POPULATION, AMERICAN JOURNAL OF HUMAN GENETICS 34: 444 (1982). / AMERICAN JOURNAL OF HUMAN GENETICS (1982)
10.1016/0378-1119(83)90230-5
HASILIK, A, BIOSYNTHESIS OF LYSOSOMAL-ENZYMES IN FIBROBLASTS - SYNTHESIS AS PRECURSORS OF HIGHER MOLECULAR-WEIGHT, JOURNAL OF BIOLOGICAL CHEMISTRY 255: 4937 (1980). (10.1016/S0021-9258(19)85585-0) / JOURNAL OF BIOLOGICAL CHEMISTRY (1980)
HODGES, P.E., AMERICAN JOURNAL OF HUMAN GENETICS 43 Supplement: A186 (1988). / AMERICAN JOURNAL OF HUMAN GENETICS (1988)
JOHNSON, W.G., JUVENILE SPINAL MUSCULAR-ATROPHY - A NEW HEXOSAMINIDASE DEFICIENCY PHENOTYPE, ANNALS OF NEUROLOGY 11: 11 (1982). (10.1002/ana.410110103) / ANNALS OF NEUROLOGY (1982)
KABACK, M.M., CLIN RES 27: 121 (1979). / CLIN RES (1979)
KOLODNY, E.H., GM2-GANGLIOSIDOSIS - HEXOSAMINIDASE MUTATIONS NOT OF THE TAY-SACHS TYPE PRODUCE UNUSUAL CLINICAL VARIANTS, TRENDS IN NEUROSCIENCES 6: 16 (1983). (10.1016/0166-2236(83)90008-5) / TRENDS IN NEUROSCIENCES (1983)
Korneluk, R. G., Journal of Biological Chemistry 261: 8407 (1986). (10.1016/S0021-9258(19)83927-3) / Journal of Biological Chemistry (1986)
10.1016/0076-6879(87)54085-X
KYTZIA, H.J., EVIDENCE FOR 2 DIFFERENT ACTIVE-SITES ON HUMAN BETA-HEXOSAMINIDASE-A - INTERACTION OF GM2 ACTIVATOR PROTEIN WITH BETA-HEXOSAMINIDASE-A, JOURNAL OF BIOLOGICAL CHEMISTRY 260: 7568 (1985). (10.1016/S0021-9258(17)39645-X) / JOURNAL OF BIOLOGICAL CHEMISTRY (1985)
MITSUMOTO, H, MOTOR NEURON DISEASE AND ADULT HEXOSAMINIDASE A DEFICIENCY IN 2 FAMILIES - EVIDENCE FOR MULTISYSTEM DEGENERATION, ANNALS OF NEUROLOGY 17: 378 (1985). (10.1002/ana.410170413) / ANNALS OF NEUROLOGY (1985)
MULLIS, K.B., SPECIFIC SYNTHESIS OF DNA INVITRO VIA A POLYMERASE-CATALYZED CHAIN-REACTION, METHODS IN ENZYMOLOGY 155: 335 (1987). (10.1016/0076-6879(87)55023-6) / METHODS IN ENZYMOLOGY (1987)
MYEROWITZ, R, THE MAJOR DEFECT IN ASHKENAZI JEWS WITH TAY-SACHS DISEASE IS AN INSERTION IN THE GENE FOR THE ALPHA-CHAIN OF BETA-HEXOSAMINIDASE, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 18587 (1988). (10.1016/S0021-9258(18)37323-X) / JOURNAL OF BIOLOGICAL CHEMISTRY (1988)
Myerowitz, R., Proceedings of the National Academy of Sciences of the United States of America 81: 5394 (1984). / Proceedings of the National Academy of Sciences of the United States of America (1984)
MYEROWITZ, R, HUMAN BETA-HEXOSAMINIDASE ALPHA-CHAIN - CODING SEQUENCE AND HOMOLOGY WITH THE BETA-CHAIN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 82: 7830 (1985). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1985)
MYEROWITZ, R, SPLICE JUNCTION MUTATION IN SOME ASHKENAZI JEWS WITH TAY-SACHS DISEASE - EVIDENCE AGAINST A SINGLE DEFECT WITHIN THIS ETHNIC-GROUP, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 3955 (1988). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1988)
NAVON, R, APPARENT DEFICIENCY OF HEXOSAMINIDASE A IN HEALTHY MEMBERS OF A FAMILY WITH TAY-SACHS DISEASE, AMERICAN JOURNAL OF HUMAN GENETICS 25: 287 (1973). / AMERICAN JOURNAL OF HUMAN GENETICS (1973)
NAVON, R, FREQUENCY OF HEXOSAMINIDASE A VARIANT ALLELES AMONG ASHKENAZI JEWS AND PRENATAL-DIAGNOSIS OF GM2 GANGLIOSIDOSIS, AMERICAN JOURNAL OF HUMAN GENETICS 37: 1031 (1985). / AMERICAN JOURNAL OF HUMAN GENETICS (1985)
NAVON, R, HEXOSAMINIDASE-A DEFICIENCY IN ADULTS, AMERICAN JOURNAL OF MEDICAL GENETICS 24: 179 (1986). (10.1002/ajmg.1320240123) / AMERICAN JOURNAL OF MEDICAL GENETICS (1986)
NAVON, R, ADULT (GM2) GANGLIOSIDOSIS - NEUROLOGIC AND BIOCHEMICAL FINDINGS IN AN APPARENTLY NEW TYPE, NEUROLOGY 30: 449 (1980). / NEUROLOGY (1980)
NAVON, R, ADULT GM2 GANGLIOSIDOSIS IN ASSOCIATION WITH TAY-SACHS DISEASE - A NEW PHENOTYPE, NEUROLOGY 31: 1397 (1981). (10.1212/WNL.31.11.1397) / NEUROLOGY (1981)
NAVON R unpublished data.
OHNO, K, A SPLICING DEFECT DUE TO AN EXON-INTRON JUNCTIONAL MUTATION RESULTS IN ABNORMAL BETA-HEXOSAMINIDASE ALPHA-CHAIN MESSENGER-RNAS IN ASHKENAZI JEWISH PATIENTS WITH TAY-SACHS DISEASE, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 153: 463 (1988). (10.1016/S0006-291X(88)81247-6) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1988)
OSHIMA, A, THE HUMAN CATION-INDEPENDENT MANNOSE 6-PHOSPHATE RECEPTOR - CLONING AND SEQUENCE OF THE FULL-LENGTH CDNA AND EXPRESSION OF FUNCTIONAL RECEPTOR IN COS CELLS, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 2553 (1988). (10.1016/S0021-9258(18)69243-9) / JOURNAL OF BIOLOGICAL CHEMISTRY (1988)
Paw, B. H., Proceedings of the National Academy of Sciences of the United States of America 86: 2413 (1989). / Proceedings of the National Academy of Sciences of the United States of America (1989)
PROIA, R.L., ORGANIZATION OF THE GENE ENCODING THE HUMAN BETA-HEXOSAMINIDASE ALPHA-CHAIN, JOURNAL OF BIOLOGICAL CHEMISTRY 262: 5677 (1987). (10.1016/S0021-9258(18)45628-1) / JOURNAL OF BIOLOGICAL CHEMISTRY (1987)
Proia, R. L., Proceedings of the National Academy of Sciences of the United States of America 79: 6360 (1982). / Proceedings of the National Academy of Sciences of the United States of America (1982)
PROIA, R.L., GENE ENCODING THE HUMAN BETA-HEXOSAMINIDASE BETA-CHAIN - EXTENSIVE HOMOLOGY OF INTRON PLACEMENT IN THE ALPHA-CHAIN AND BETA-CHAIN GENES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 1883 (1988). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1988)
RAPIN, I, ADULT (CHRONIC) GM2 GANGLIOSIDOSIS - ATYPICAL SPINOCEREBELLAR DEGENERATION IN A JEWISH SIBSHIP, ARCHIVES OF NEUROLOGY 33: 120 (1976). (10.1001/archneur.1976.00500020048008) / ARCHIVES OF NEUROLOGY (1976)
10.1126/science.2999980
Sandhoff, K., The Metabolic Basis of Inherited Disease: 1807 (1988). / The Metabolic Basis of Inherited Disease (1988)
10.1073/pnas.74.12.5463
Young, R. A., Proceedings of the National Academy of Sciences of the United States of America 80: 1194 (1983). / Proceedings of the National Academy of Sciences of the United States of America (1983)

Dates

Type	When
Created	18 years, 11 months ago (Oct. 5, 2006, 5:21 p.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 10:10 a.m.)
Indexed	6 days, 6 hours ago (Aug. 30, 2025, 12:59 p.m.)
Issued	36 years, 5 months ago (March 17, 1989)
Published	36 years, 5 months ago (March 17, 1989)
Published Print	36 years, 5 months ago (March 17, 1989)

Funders 0

None

BibTeX

@article{Navon_1989, title={The Mutations in Ashkenazi Jews with Adult G M2 Gangliosidosis, the Adult Form of Tay-Sachs Disease}, volume={243}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2522679}, DOI={10.1126/science.2522679}, number={4897}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Navon, Ruth and Proia, Richard L.}, year={1989}, month=mar, pages={1471–1474} }

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      "key": "e_1_2_1_29_1",
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      "journal-title": "AMERICAN JOURNAL OF HUMAN GENETICS"
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      "journal-title": "AMERICAN JOURNAL OF MEDICAL GENETICS"
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