J Korean Med Sci.  2005 Jun;20(3):499-501. 10.3346/jkms.2005.20.3.499.

A Novel Mutation (A148V) in the Glucose 6-phosphate Translocase (SLC37A4) Gene in a Korean Patient with Glycogen Storage Disease Type 1b

• Han SH
• Ki CS
• Lee JE
• Hong YJ
• Son BK
• Lee KH
• Choe YH
• Lee SY
• Kim JW

• KMID: 1778514
• DOI: http://doi.org/10.3346/jkms.2005.20.3.499

Abstract

We report a Korean patient with glycogen storage disease type 1b (GSD-1b) whose diagnosis was confirmed by liver biopsy and laboratory results. The patient presented with delay of puberty and short stature on admission and had typical clinical symptoms of GSD as well as chronic neutropenia and inflammatory bowel disease. Mutation analysis of the glucose 6-phosphate translocase 6-phosphate translocase (SLC37A4) gene revealed that the patient was a compound heterozygote of two different mutations including a deletion mutation (c.1042_1043delCT; L348fs) and a missense mutation (A148V). The L348fs mutation was inherited from the patient's father and has been reported in an Italian family with GSD-1b, while the A148V mutation was transmitted from the patient's mother and was a novel mutation. To the best of our knowledge, this is the first report of genetically confirmed case of GSD-1b in Korean.

Keyword

Glycogen Storage Disease; Glycogen Storage Disease Type 1; GSD-1b; Genes; SLC37A4 Gene; Mutation

MeSH Terms

Base Sequence
DNA/chemistry/genetics
DNA Mutational Analysis
Glycogen Storage Disease Type I/enzymology/*genetics
Humans
Korea
*Mutation, Missense
Phosphotransferases/*genetics
Research Support, Non-U.S. Gov't

Figure

• 

  Fig. 1 Identification of SLC37A4 gene mutations. (A) Direct sequencing analysis demonstrated a heterozygous C to T transition (arrow; c.443C>T) resulting in a A148V missense mutation was observed in exon 3. (B) A heterozygous 2-bp deletion (arrow; c.1042-1043delCT) resulting in a A347fs×400 mutation in exon 8. Because the sequencing was performed with an anti-sense primer, overlapped peaks appear from the C+G peaks (arrow).

Reference

1. Gerin I, Veiga-da-Cunha M, Achouri Y, Collet JF, Van Schaftingen E. Sequence of a putative glucose 6-phosphate translocase, mutated in glycogen storage disease type Ib. FEBS Lett. 1997. 419:235–238.

2. Veiga-da-Cunha M, Gerin I, Chen YT, de Barsy T, de Lonlay P, Dionisi-Vici C, Fenske CD, Lee PJ, Leonard JV, Maire I, McConkie-Rosell A, Schweitzer S, Vikkula M, Van Schaftingen E. A gene on chromosome 11q23 coding for a putative glucose-6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. Am J Hum Genet. 1998. 63:976–983.

3. Galli L, Orrico A, Marcolongo P, Fulceri R, Burchell A, Melis D, Parini R, Gatti R, Lam C, Benedetti A, Sorrentino V. Mutations in the glucose-6-phosphate transporter (G6PT) gene in patients with glycogen storage diseases type 1b and 1c. FEBS Lett. 1999. 459:255–258.

4. Veiga-da-Cunha M, Gerin I, Chen YT, Lee PJ, Leonard JV, Maire I, Wendel U, Vikkula M, Van Schaftingen E. The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. Eur J Hum Genet. 1999. 7:717–723.

5. Lam CW, Sin SY, Lau ET, Lam YY, Poon P, Tong SF. Prenatal diagnosis of glycogen storage disease type 1b using denaturing high performance liquid chromatography. Prenat Diagn. 2000. 20:765–768.

6. Marcolongo P, Barone V, Priori G, Pirola B, Giglio S, Biasucci G, Zammarchi E, Parenti G, Burchell A, Benedetti A, Sorrentino V. Structure and mutation analysis of the glycogen storage disease type 1b gene. FEBS Lett. 1998. 436:247–250.

7. Chen YT, Bruchell A. Scriver CR, Beaudet AL, Sly WS, Valle D, editors. Glycogen storage disease. The Metabolic and Molecular Bases of Inherited Disease. 7th edn. McGraw-Hill;395–965.

8. Lei KJ, Pan CJ, Shelly LL, Liu JL, Chou JY. Identification of mutations in the gene for glucose-6-phosphatase, the enzyme deficient in glycogen storage disease type 1a. J Clin Invest. 1994. 93:1994–1999.

9. Beaudet AL, Anderson DC, Michels VV, Arion WJ, Lange AJ. Neutropenia and impaired neutrophil migration in type IB glycogen storage disease. J Pediatr. 1980. 97:906–910.

10. Kure S, Suzuki Y, Matsubara Y, Sakamoto O, Shintaku H, Isshiki G, Hoshida C, Izumi I, Sakura N, Narisawa K. Molecular analysis of glycogen storage disease type Ib: identification of a prevalent mutation among Japanese patients and assignment of a putative glucose-6-phosphate translocase gene to chromosome 11. Biochem Biophys Res Commun. 1998. 248:426–431.

11. Gerin I, Veiga-da-Cunha M, Noel G, Van Schaftingen E. Structure of the gene mutated in glycogen storage disease type Ib. Gene. 1999. 227:189–195.

12. Hiraiwa H, Pan CJ, Lin B, Moses SW, Chou JY. Inactivation of the glucose 6-phosphate transporter causes glycogen storage disease type 1b. J Biol Chem. 1999. 274:5532–5536.

13. Janecke AR, Bosshard NU, Mayatepek E, Schulze A, Gitzelmann R, Burchell A, Bartram CR, Janssen B. Molecular diagnosis of type 1c glycogen storage disease. Human Genet. 1999. 104:275–277.

14. Chen LY, Pan CJ, Shieh JJ, Chou JY. Structure-function analysis of the glucose-6 phosphate transporter deficient in glycogen storage disease type Ib. Hum Mol Genet. 2002. 11:3199–3207.