A gene on chromosome 11q23 coding for a putative glucose-6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic

Maria Veiga-da-Cunha, Isabelle Gerin, Yuan Tsong Chen, Thierry De Barsy, Pascale De Lonlay, Carlo Dionisi-Vici, Christiane D. Fenske, Philip J. Lee, James V. Leonard, Iréne Maire, Allyn McConkie-Rosell, Susanne Schweitzer, Miikka Vikkula, Emile Van Schaftingen

Research output: Contribution to journalArticle

Abstract

Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose-6-phosphatase, an enzymatic system present in the endoplasmic reticulum that plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib and Ic are not due to mutations in the phosphohydrolase gene and are clinically characterized by the presence of associated neutropenia and neutrophil dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6-phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in the microsomes. We have recently cloned a cDNA encoding a putative glucose-6-phosphate translocase. We have now localized the corresponding gene on chromosome 11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis and sequencing, we have screened this gene, for mutations in genomic DNA, from patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations found, 11 result in truncated proteins that are probably nonfunctional. Most other mutations result in substitutions of conserved or semiconserved residues. The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute ~40% of the disease alleles. The fact that the same mutations are found in GSD types Ib and Ic could indicate either that Pi and glucose-6-phosphate are transported in microsomes by the same transporter or that the biochemical assays used to differentiate Pi and glucose-6-phosphate transport defects are not reliable.

Original languageEnglish
Pages (from-to)976-983
Number of pages8
JournalAmerican Journal of Human Genetics
Volume63
Issue number4
DOIs
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Genetics

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    Veiga-da-Cunha, M., Gerin, I., Chen, Y. T., De Barsy, T., De Lonlay, P., Dionisi-Vici, C., Fenske, C. D., Lee, P. J., Leonard, J. V., Maire, I., McConkie-Rosell, A., Schweitzer, S., Vikkula, M., & Van Schaftingen, E. (1998). A gene on chromosome 11q23 coding for a putative glucose-6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. American Journal of Human Genetics, 63(4), 976-983. https://doi.org/10.1086/302068