Identification of p.His119Leu mutation in the<i> G6PC</i> gene of a Vietnamese patient with glycogen storage disease type Ia

Nguyen Huy Hoang; Vu Chi Dung; Nguyen Van Tung; Nguyen Ngoc Lan; Ha Thi Dung

doi:10.15625/2615-9023/v42n2.14898

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Authors

Nguyen Huy Hoang
Vu Chi Dung
Nguyen Van Tung
Nguyen Ngoc Lan
Ha Thi Dung

DOI:

https://doi.org/10.15625/2615-9023/v42n2.14898

Keywords:

G6PC gene, Glycogen storage disease type Ia, mutation p.His119Leu, rare disease, whole exome sequencing.

Abstract

Glycogen storage disease type Ia (GSD Ia), a rare autosomal inherited disorder, is characterized by accumulation of excessive glycogen and fat in the liver. Primary symptoms of GSD Ia include hypoglycemia; metabolic acidosis; elevated levels of lactate, uric acid and lipids; hepatomagaly and growth retardation. Glycogen storage disease type Ia was caused by mutations in the G6PC gene. In this study, mutations in a Vietnamese patient with glycogen storage disease type Ia were analyzed using the whole exome sequencing method. A missense mutation c.356A>T (p.His119Leu) in the G6PC gene of the patient was identified in exon 3. Genetic analysis confirmed that this mutation was present under homozygous form In-silico analyses using SIFT and Mutation Taster confirmed the damaging effects of this mutations on the function of the proteins. This result enriches knowledge of the G6PC gene mutation spectrum and provides genetic data for further studies on glycogen storage disease type Ia in Viet Nam.

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References

Akanuma J., Nishigaki T., Fujii K., Matsubara Y., Inui K., Takahashi K., Kure S., Suzuki Y., Ohura T., Miyabayashi S., Ogawa E., Iinuma K., Okada S., Narisawa K., 2000. Glycogen storage disease type Ia: Molecular diagnosis of 51 Japanese patients and characterization of splicing mutations by analysis of ectopically transcribed mRNA from lymphoblastoid cells. Am. J. Med. Genet., 91(2): 107–112.

Bali D. S., Chen Y. T., Austin S., Goldstein J. L., 1993. Glycogen Storage Disease Type I. In: Adam M. P., Ardinger H. H., Pagon R. A., Wallace S. E., Bean L. J., Stephens K., Amemiya A., (Eds). GeneReviews®. Seattle (WA): University of Washington, Seattle.

Chou J. Y., Mansfield B. C. 2008. Mutations in the Glucose-6-Phosphatase-α (G6PC) Gene that Cause Type Ia Glycogen Storage Disease. Hum. Mutat., 29(7): 921–930.

Chou J. Y., Matern D., Mansfield B. C., Chen Y. T. 2002. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex. Curr. Mol. Med., 2(2): 121–143.

Froissart R., Piraud M., Boudjemline A. M., Vianey.Saban C., Petit F., Hubert. Buron A., Eberschweiler P. T., Gajdos V., Labrune P., 2011. Glucose-6-phosphatase deficiency. Orphanet. J. Rare Dis. 6: 27.

Gu L. L., Li X. H., Han Y., Zhang D. H., Gong Q. M., Zhang X. X. 2014. A novel homozygous no-stop mutation in G6PC gene from a Chinese patient with glycogen storage disease type Ia. Gene, 536(2): 362–365.

Hemrika W., Wever R., 1997. A new model for the membrane topology of glucose-6-phosphatase: the enzyme involved in von Gierke disease. FEBS Lett., 409(3): 317–319.

Hicks J., Wartchow E., Mierau G., 2011. Glycogen storage diseases: a brief review and update on clinical features., genetic abnormalities., pathologic features., and treatment. Ultrastruct. Pathol., 35(5): 183–196.

Karthi S., Manimaran P., Varalakshmi P., Ganesh R., Kapoor S., Goyal M., Ashokkumar B., 2019. Mutational spectrum and identification of five novel mutations in G6PC1 gene from a cohort of Glycogen Storage Disease Type 1a. Gene, 700: 7–16.

Lei K. J., Pan C. J., Liu J. L., Shelly L. L., Chou, J. Y., 1995. Structure Function Analysis of Human Glucose6phosphatase, the Enzyme Deficient in Glycogen Storage Disease Type 1a. J. Biol. Chem., 270: 11882–11886

Li H., Durbin R., 2009. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinforma. Oxf. Engl., 25(14): 1754–1760.

McKenna A., Hanna M., Banks E., Sivachenko A., Cibulskis K., Kernytsky A., Garimella K., Altshuler D., Gabriel S., Daly M., DePristo M. A., 2010. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res., 20(9): 1297–1303.

Ng P. C., Henikoff S., 2003. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res., 31(13): 3812–3814.

Ozen H., 2007. Glycogen storage diseases: new perspectives. World J. Gastroenterol.. 13(18): 2541–2553.

Pan C. J., Lei K. J., Annabi B., Hemrika W., Chou J. Y., 1998. Transmembrane topology of glucose-6-phosphatase. J. Biol. Chem., 273(11): 6144–6148.

Rake J. P., Visser G., Labrune P., Leonard J. V., Ullrich K., Smit G. P. A., 2002. Glycogen storage disease type I: diagnosis., management., clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). Eur. J. Pediatr., 161 Suppl 1: S20-34.

Rake J. P., Visser G., Smit G. P. A., 2006. Disorders of Carbohydrate and Glycogen Metabolism. In: Blau N., Leonard J., Hoffmann G. F., Clarke J. T. R., editors. Physician’s Guide Treat Follow- Metab Dis Roach PJ. 2002. Glycogen and its metabolism. Curr. Mol. Med., 2(2): 101–120.

Saltik I. N., Ozen H., Ciliv G., Koçak N., Yüce A., Gürakan F., Dinler G., 2000. Glycogen storage disease type Ia: frequency and clinical course in Turkish children. Indian J. Pediatr., 67(7): 497–501.

Schwarz J. M., Cooper D. N., Schuelke M., Seelow D., 2014. MutationTaster2: mutation prediction for the deep-sequencing age. Nat. Methods., 11(4): 361–362.

Shieh J. J., Lu Y. H., Huang S. W., Huang Y. H., Sun C. H., Chiou H. J., Liu C., Lo M. Y., Lin C. Y., Niu D. M., 2012. Misdiagnosis as steatohepatitis in a family with mild glycogen storage disease type 1a. Gene, 509(1): 154–157.

Shieh J. J., Terzioglu M., Hiraiwa H., Marsh J., Pan C. J., Chen L. Y., Chou J. Y., 2002. The molecular basis of glycogen storage disease type 1a: structure and function analysis of mutations in glucose-6-phosphatase. J. Biol. Chem., 277(7): 5047–5053.

Stukey J., Carman G. M., 1997. Identification of a novel phosphatase sequence motif. Protein Sci. Publ. Protein Soc., 6(2): 469–472.

Wolfsdorf J. I., Weinstein D. A, 2003. Glycogen storage diseases. Rev. Endocr. Metab. Disord., 4(1): 95–102.

Wu M. C., Tsai F. J., Lee C. C., Tsai C. H., Wu J. Y., 2000. A novel missense mutation (H119L) identified in a Taiwan Chinese family with glycogen storage disease type 1a (von Gierke disease) Human Mutat., 16: 447.