Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene
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Yu Ding
und
Xiumin Wang
Abstract
Background
The phosphoglucomutase 1 (PGM1) enzyme plays a central role in glucose homeostasis by catalyzing the inter-conversion of glucose 1-phosphate and glucose 6-phosphate. Recently, PGM1 deficiency has been recognized as a cause of the congenital disorders of glycosylation (CDGs).
Methods
Two Chinese Han pediatric patients with recurrent hypoglycemia, hepatopathy and growth retardation are described in this study. Targeted gene sequencing (TGS) was performed to screen for causal genetic variants in the genome of the patients and their parents to determine the genetic basis of the phenotype.
Results
DNA sequencing identified three variations of the PGM1 gene (NM_002633.2). Patient 1 had a novel homozygous mutation (c.119delT, p.Ile40Thrfs*28). In patient 2, we found a compound heterozygous mutation of c.1172G>T(p.Gly391Val) (novel) and c.1507C>T(p.Arg503*) (known pathogenic).
Conclusions
This report deepens our understanding of the clinical features of PGM1 mutation. The early molecular genetic analysis and multisystem assessment were here found to be essential to the diagnosis of PGM1-CDG and the provision of timely and proper treatment.
Acknowledgments
The authors of the study would like to thank the patients and their families for participating in the present study. We would like to thank Accdon (www.accdon.com) for its linguistic assistance during the preparation of this manuscript.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by the National Natural Science Foundation of China (grant nos. 81370930, 81201353 and 81472051) and Cross Research Fund for Medical Engineering of Shanghai Jiao Tong University (grant no. YG2016QN39).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Timal S, Hoischen A, Lehle L, Adamowicz M, Huijben K, et al. Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing. Hum Mol Genet 2012;21:4151–61.10.1093/hmg/dds123Suche in Google Scholar PubMed
2. Beamer LJ. Mutations in hereditary phosphoglucomutase 1 deficiency map to key regions of enzyme structure and function. J Inherit Metab Dis 2015;38:243–56.10.1007/s10545-014-9757-9Suche in Google Scholar PubMed
3. Tegtmeyer LC, Rust S, van Scherpenzeel M, Ng BG, Losfeld ME, et al. Multiple phenotypes in phosphoglucomutase 1 deficiency. N Engl J Med 2014;370:533–42.10.1056/NEJMoa1206605Suche in Google Scholar PubMed PubMed Central
4. Zeevaert R, Scalais E, Muino Mosquera L, De Meirleir L, De Beaufort C, et al. PGM1 deficiency diagnosed during an endocrine work-up of low IGF-1 mediated growth failure. Acta Clin Belg 2016;71:435–7.10.1080/17843286.2016.1142043Suche in Google Scholar PubMed
5. Ondruskova N, Honzik T, Vondrackova A, Tesarova M, Zeman J, et al. Glycogen storage disease-like phenotype with central nervous system involvement in a PGM1-CDG patient. Neuro Endocrinol Lett 2014;35:137–41.Suche in Google Scholar
6. Li N, Chang G, Xu Y, Ding Y, Li G, et al. Clinical and molecular characterization of patients with fructose 1,6-bisphosphatase deficiency. Int J Mol Sci 2017;18:857.10.3390/ijms18040857Suche in Google Scholar PubMed PubMed Central
7. Richards S, Aziz N, Bale S, Bick D, Das S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–24.10.1038/gim.2015.30Suche in Google Scholar PubMed PubMed Central
8. Wong SY, Gadomski T, van Scherpenzeel M, Honzik T, Hansikova H, et al. Oral D-galactose supplementation in PGM1-CDG. Genet Med 2017;19:1226–35.10.1038/gim.2017.41Suche in Google Scholar PubMed PubMed Central
9. Morava E. Galactose supplementation in phosphoglucomutase-1 deficiency; review and outlook for a novel treatable CDG. Mol Genet Metab 2014;112:275–9.10.1016/j.ymgme.2014.06.002Suche in Google Scholar PubMed PubMed Central
10. Stojkovic T, Vissing J, Petit F, Piraud M, Orngreen MC, et al. Muscle glycogenosis due to phosphoglucomutase 1 deficiency. N Engl J Med 2009;361:425–7.10.1056/NEJMc0901158Suche in Google Scholar PubMed
11. Wong SY, Beamer LJ, Gadomski T, Honzik T, Mohamed M, et al. Defining the phenotype and assessing severity in phosphoglucomutase-1 deficiency. J Pediatr 2016;175:130–6 e138.10.1016/j.jpeds.2016.04.021Suche in Google Scholar PubMed
12. Rymen D, Winter J, Van Hasselt PM, Jaeken J, Kasapkara C, et al. Key features and clinical variability of COG6-CDG. Mol Genet Metab 2015;116:163–70.10.1016/j.ymgme.2015.07.003Suche in Google Scholar PubMed
13. Ferens-Sieczkowska M, Zwierz K, Midro A, Katnik-Prastowska I. Glycoforms of six serum glycoproteins in a patient with congenital disorder of glycosylation type I. Arch Immunol Ther Exp 2002;50:67–73.Suche in Google Scholar
14. Theodore M, Morava E. Congenital disorders of glycosylation: sweet news. Curr Opin Pediatr 2011;23:581–7.10.1097/MOP.0b013e32834cd693Suche in Google Scholar PubMed
15. Stanley CA. Perspective on the genetics and diagnosis of congenital hyperinsulinism disorders. J Clin Endocrinol Metab 2016;101:815–26.10.1210/jc.2015-3651Suche in Google Scholar PubMed PubMed Central
16. Loewenthal N, Haim A, Parvari R, Hershkovitz E. Phosphoglucomutase-1 deficiency: intrafamilial clinical variability and common secondary adrenal insufficiency. Am J Med Genet A 2015;167A:3139–43.10.1002/ajmg.a.37294Suche in Google Scholar PubMed
17. Takahashi A, Mizusawa K. Posttranslational modifications of proopiomelanocortin in vertebrates and their biological significance. Front Endocrinol 2013;4:143.10.3389/fendo.2013.00143Suche in Google Scholar PubMed PubMed Central
18. Lane L, Argoud-Puy G, Britan A, Cusin I, Duek PD, et al. neXtProt: a knowledge platform for human proteins. Nucleic Acids Res 2012;40(Database issue):D76–83.10.1093/nar/gkr1179Suche in Google Scholar PubMed PubMed Central
19. Putt W, Ives JH, Hollyoake M, Hopkinson DA, Whitehouse DB, et al. Phosphoglucomutase 1: a gene with two promoters and a duplicated first exon. Biochem J 1993;296(Pt 2):417–22.10.1042/bj2960417Suche in Google Scholar PubMed PubMed Central
20. Scott K, Gadomski T, Kozicz T, Morava E. Congenital disorders of glycosylation: new defects and still counting. J Inherit Metab Dis 2014;37:609–17.10.1007/s10545-014-9720-9Suche in Google Scholar PubMed PubMed Central
21. Voermans NC, Preisler N, Madsen KL, Janssen MC, Kusters B, et al. PGM1 deficiency: substrate use during exercise and effect of treatment with galactose. Neuromusc Disord 2017;27:370–6.10.1016/j.nmd.2017.01.014Suche in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
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- Original Articles
- Can having a sibling with type 1 diabetes cause disordered eating behaviors?
- Wrist circumference as a novel predictor of obesity in children and adolescents: the CASPIAN-IV study
- Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance
- Impact of a group-based treatment program on adipocytokines, oxidative status, inflammatory cytokines and arterial stiffness in obese children and adolescents
- Clinical management of childhood hyperthyroidism with and without Down syndrome: a longitudinal study at a single center
- Detection of distant metastasis at the time of ablation in children with differentiated thyroid cancer: the value of pre-ablation stimulated thyroglobulin
- Random serum free cortisol and total cortisol measurements in pediatric septic shock
- Self-assessment of pubertal development in a puberty cohort
- Growth, the Mediterranean diet and the buying power of adolescents in Greece
- Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene
- Genetic analysis of three families with X-linked dominant hypophosphatemic rickets
- Clinical heterogeneity and molecular profile of triple A syndrome: a study of seven cases
- No central adrenal insufficiency found in patients with Prader-Willi syndrome with an overnight metyrapone test
- Case Reports
- A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index
- Hypertriglyceridemia thalassemia syndrome
- Severe consumptive hypothyroidism caused by multiple infantile hepatic haemangiomas
Artikel in diesem Heft
- Frontmatter
- Review
- Prevalence of cranial MRI findings in girls with central precocious puberty: a systematic review and meta-analysis
- Original Articles
- Can having a sibling with type 1 diabetes cause disordered eating behaviors?
- Wrist circumference as a novel predictor of obesity in children and adolescents: the CASPIAN-IV study
- Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance
- Impact of a group-based treatment program on adipocytokines, oxidative status, inflammatory cytokines and arterial stiffness in obese children and adolescents
- Clinical management of childhood hyperthyroidism with and without Down syndrome: a longitudinal study at a single center
- Detection of distant metastasis at the time of ablation in children with differentiated thyroid cancer: the value of pre-ablation stimulated thyroglobulin
- Random serum free cortisol and total cortisol measurements in pediatric septic shock
- Self-assessment of pubertal development in a puberty cohort
- Growth, the Mediterranean diet and the buying power of adolescents in Greece
- Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene
- Genetic analysis of three families with X-linked dominant hypophosphatemic rickets
- Clinical heterogeneity and molecular profile of triple A syndrome: a study of seven cases
- No central adrenal insufficiency found in patients with Prader-Willi syndrome with an overnight metyrapone test
- Case Reports
- A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index
- Hypertriglyceridemia thalassemia syndrome
- Severe consumptive hypothyroidism caused by multiple infantile hepatic haemangiomas
