DOI: 10.1126/science.8211187. Mutations in the Glucose-6-Phosphatase Gene that Cause Glycogen Storage Disease Type 1a

Mutations in the Glucose-6-Phosphatase Gene that Cause Glycogen Storage Disease Type 1a

10.1126/science.8211187

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Glycogen storage disease (GSD) type 1a is caused by the deficiency of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.

Bibliography

Lei, K.-J., Shelly, L. L., Pan, C.-J., Sidbury, J. B., & Chou, J. Y. (1993). Mutations in the Glucose-6-Phosphatase Gene that Cause Glycogen Storage Disease Type 1a. Science, 262(5133), 580â583.

Authors 5

Ke-Jian Lei (first)
Leslie L. Shelly (additional)
Chi-Jiunn Pan (additional)
James B. Sidbury (additional)
Janice Yang Chou (additional)

References 24 Referenced 306

ARION, W.J., SPECIFICITY OF GLUCOSE 6-PHOSPHATASE OF INTACT LIVER-MICROSOMES, JOURNAL OF BIOLOGICAL CHEMISTRY 247: 2558 (1972). (10.1016/S0021-9258(19)45462-8) / JOURNAL OF BIOLOGICAL CHEMISTRY (1972)
ARION, W.J., GLUCOSE-6-PHOSPHATE TRANSPORT AND MICROSOMAL GLUCOSE-6-PHOSPHATASE .6. EVIDENCE FOR THE PARTICIPATION OF INDEPENDENT TRANSLOCASES FOR PHOSPHATE AND GLUCOSE-6-PHOSPHATE IN THE MICROSOMAL GLUCOSE-6-PHOSPHATASE SYSTEM - INTERACTIONS OF THE SYSTEM WITH ORTHO-PHOSPHATE, INORGANIC PYROPHOSPHATE, AND CARBAMYL-PHOSPHATEE, JOURNAL OF BIOLOGICAL CHEMISTRY 255: 396 (1980). / JOURNAL OF BIOLOGICAL CHEMISTRY (1980)
Beaudet A. L. Harrison's Principles of Internal Medicine 12 1854 (1991).
BURCHELL, A, A NEW MICROTECHNIQUE FOR THE ANALYSIS OF THE HUMAN HEPATIC-MICROSOMAL GLUCOSE-6-PHOSPHATASE SYSTEM, CLINICA CHIMICA ACTA 173: 183 (1988). (10.1016/0009-8981(88)90256-2) / CLINICA CHIMICA ACTA (1988)
COUNTAWAY, J.L., THE PHOSPHOHYDROLASE COMPONENT OF THE HEPATIC-MICROSOMAL GLUCOSE-6-PHOSPHATASE SYSTEM IS A 36.5-KILODALTON POLYPEPTIDE, JOURNAL OF BIOLOGICAL CHEMISTRY 263: 2673 (1988). (10.1016/S0021-9258(18)69120-3) / JOURNAL OF BIOLOGICAL CHEMISTRY (1988)
GLUECKSOHNWAELS.S, GENETIC-CONTROL OF MORPHOGENETIC AND BIOCHEMICAL DIFFERENTIATION - LETHAL ALBINO DELETIONS IN THE MOUSE, CELL 16: 225 (1979). (10.1016/0092-8674(79)90001-1) / CELL (1979)
HEIJNE, G.V., NUCLEIC ACIDS RES 14: 4683 (1986). (10.1093/nar/14.11.4683) / NUCLEIC ACIDS RES (1986)
Hers, H. G., Advances in Metabolic Disorders 1: 1 (1964). (10.1016/B978-1-4831-6748-0.50006-9) / Advances in Metabolic Disorders (1964)
Hers, H. G., The Metabolic Basis of Inherited Diseases: 425 (1989). / The Metabolic Basis of Inherited Diseases (1989)
HOLLIDAY, R, DNA METHYLATION AND MUTATION, MUTATION RESEARCH 285: 61 (1993). (10.1016/0027-5107(93)90052-H) / MUTATION RESEARCH (1993)
JACKSON, M.R., IDENTIFICATION OF A CONSENSUS MOTIF FOR RETENTION OF TRANSMEMBRANE PROTEINS IN THE ENDOPLASMIC-RETICULUM, EMBO JOURNAL 9: 3153 (1990). (10.1002/j.1460-2075.1990.tb07513.x) / EMBO JOURNAL (1990)
JORGENSON, R.A., MULTIFUNCTIONAL GLUCOSE-6-PHOSPHATASE STUDIED IN PERMEABLE ISOLATED HEPATOCYTES, JOURNAL OF BIOLOGICAL CHEMISTRY 255: 5907 (1980). (10.1016/S0021-9258(19)70717-0) / JOURNAL OF BIOLOGICAL CHEMISTRY (1980)
KLEIN, P, THE DETECTION AND CLASSIFICATION OF MEMBRANE-SPANNING PROTEINS, BIOCHIMICA ET BIOPHYSICA ACTA 815: 468 (1985). (10.1016/0005-2736(85)90375-X) / BIOCHIMICA ET BIOPHYSICA ACTA (1985)
10.1016/0022-2836(82)90515-0
LANGE, A.J., TYPE-IB GLYCOGEN-STORAGE DISEASE IS CAUSED BY A DEFECT IN THE GLUCOSE-6-PHOSPHATE TRANSLOCASE OF THE MICROSOMAL GLUCOSE-6-PHOSPHATASE SYSTEM, JOURNAL OF BIOLOGICAL CHEMISTRY 255: 8381 (1980). (10.1016/S0021-9258(18)43502-8) / JOURNAL OF BIOLOGICAL CHEMISTRY (1980)
LEI J.K. unpublished data.
Nordlie R. C. The Enzymes of Biological Membranes 2: 349 (1985). (10.1007/978-1-4613-2355-6_11)
NORDLIE, R.C., J BIOL CHEM 258: 8739 (1983). (10.1016/S0021-9258(18)32118-5) / J BIOL CHEM (1983)
RIPLEY, L.S., FRAMESHIFT MUTATION - DETERMINANTS OF SPECIFICITY, ANNUAL REVIEW OF GENETICS 24: 189 (1990). (10.1146/annurev.ge.24.120190.001201) / ANNUAL REVIEW OF GENETICS (1990)
RUPPERT, S, 2 GENETICALLY DEFINED TRANS-ACTING LOCI COORDINATELY REGULATE OVERLAPPING SETS OF LIVER-SPECIFIC GENES, CELL 61: 895 (1990). (10.1016/0092-8674(90)90200-X) / CELL (1990)
SCHULZE, H.U., EVIDENCE FOR CHANGES IN THE CONFORMATIONAL STATUS OF RAT-LIVER MICROSOMAL GLUCOSE-6-PHOSPHATE - PHOSPHOHYDROLASE DURING DETERGENT-DEPENDENT MEMBRANE MODIFICATION - EFFECT OF PARA-MERCURIBENZOATE AND ORGANOMERCURIAL AGAROSE-GEL ON GLUCOSE-6-PHOSPHATASE OF NATIVE AND DETERGENT-MODIFIED MICROSOMES, JOURNAL OF BIOLOGICAL CHEMISTRY 261: 16571 (1986). (10.1016/S0021-9258(18)66605-0) / JOURNAL OF BIOLOGICAL CHEMISTRY (1986)
SHELLY L.L. unpublished data.
SINGH, J, VANADATE - A POTENT INHIBITOR OF MULTIFUNCTIONAL GLUCOSE-6-PHOSPHATASE, BIOCHIMICA ET BIOPHYSICA ACTA 678: 477 (1981). (10.1016/0304-4165(81)90129-X) / BIOCHIMICA ET BIOPHYSICA ACTA (1981)
WADDELL, I.D., TRANSVERSE TOPOLOGY OF GLUCOSE-6-PHOSPHATASE IN RAT HEPATIC ENDOPLASMIC-RETICULUM, BIOCHEMICAL JOURNAL 275: 133 (1991). (10.1042/bj2750133) / BIOCHEMICAL JOURNAL (1991)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 7:05 p.m.)
Deposited	1 year, 7 months ago (Jan. 15, 2024, 5:40 a.m.)
Indexed	1 hour, 52 minutes ago (Sept. 4, 2025, 9:40 a.m.)
Issued	31 years, 10 months ago (Oct. 22, 1993)
Published	31 years, 10 months ago (Oct. 22, 1993)
Published Print	31 years, 10 months ago (Oct. 22, 1993)

Funders 0

None

BibTeX

@article{Lei_1993, title={Mutations in the Glucose-6-Phosphatase Gene that Cause Glycogen Storage Disease Type 1a}, volume={262}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.8211187}, DOI={10.1126/science.8211187}, number={5133}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lei, Ke-Jian and Shelly, Leslie L. and Pan, Chi-Jiunn and Sidbury, James B. and Chou, Janice Yang}, year={1993}, month=oct, pages={580–583} }

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