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http://dx.doi.org/10.5734/JGM.2021.18.2.132

A rare, likely pathogenic GCK variant related to maturity-onset diabetes of the young type 2: A case report  

So, Min-Kyung (Department of Laboratory Medicine, Ewha Womans University College of Medicine)
Huh, Jungwon (Department of Laboratory Medicine, Ewha Womans University College of Medicine)
Kim, Hae Soon (Department of Pediatrics, Ewha Womans University College of Medicine)
Publication Information
Journal of Genetic Medicine / v.18, no.2, 2021 , pp. 132-136 More about this Journal
Abstract
Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant pathogenic variants in one of 14 currently known monogenic genes. Characteristics of patients with MODY include early-onset clinical disease with a family history of diabetes and negative autoantibodies and may present with heterogeneous phenotypes according to the different subtypes. Here, we report a patient with early-onset diabetes who presented asymptomatic mild fasting hyperglycemia with the absence of autoantibodies. She was diagnosed with glucokinase (GCK)-MODY caused by a GCK variant, c.1289T>C (p.L430P), identified by targeted gene-panel testing, and the affected father had the same variant. We interpreted this rare missense variant as a likely pathogenic variant and then she stopped taking oral medication. This case highlights the usefulness of gene-panel testing for accurate diagnosis and appropriate management of MODY. We also note the importance of familial genetic testing and genetic counseling for the proper interpretation of MODY variants.
Keywords
Maturity-onset diabetes of the young; Glucokinase; Genetic testin;
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1 Sanyoura M, Philipson LH, Naylor R. Monogenic diabetes in children and adolescents: recognition and treatment options. Curr Diab Rep 2018;18:58.   DOI
2 Hattersley AT, Greeley SAW, Polak M, Rubio-Cabezas O, Njolstad PR, Mlynarski W, et al. ISPAD clinical practice consensus guidelines 2018: the diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2018;19 Suppl 27:47-63.   DOI
3 Li M, Wang S, Xu K, Chen Y, Fu Q, Gu Y, et al. High prevalence of a monogenic cause in Han Chinese diagnosed with type 1 diabetes, partly driven by nonsyndromic recessive WFS1 mutations. Diabetes 2020;69:121-6.   DOI
4 Carmody D, Naylor RN, Bell CD, Berry S, Montgomery JT, Tadie EC, et al. GCK-MODY in the US National Monogenic Diabetes Registry: frequently misdiagnosed and unnecessarily treated. Acta Diabetol 2016;53:703-8.   DOI
5 Brnich SE, Abou Tayoun AN, Couch FJ, Cutting GR, Greenblatt MS, Heinen CD, et al.; Clinical Genome Resource Sequence Variant Interpretation Working Group. Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework. Genome Med 2019;12:3.   DOI
6 Garber KB, Vincent LM, Alexander JJ, Bean LJH, Bale S, Hegde M. Reassessment of genomic sequence variation to harmonize interpretation for personalized medicine. Am J Hum Genet 2016;99:1140-9.   DOI
7 Donath X, Saint-Martin C, Dubois-Laforgue D, Rajasingham R, Mifsud F, Ciangura C, et al.; Monogenic Diabetes Study Group of the Societe Francophone du Diabete. Next-generation sequencing identifies monogenic diabetes in 16% of patients with late adolescence/adult-onset diabetes selected on a clinical basis: a cross-sectional analysis. BMC Med 2019;17:132.   DOI
8 Tatsi EB, Kanaka-Gantenbein C, Scorilas A, Chrousos GP, Sertedaki A. Next generation sequencing targeted gene panel in Greek MODY patients increases diagnostic accuracy. Pediatr Diabetes 2020;21:28-39.   DOI
9 Ellard S, Baple EL, Callaway A, Berry I, Forrester N, Turnbull C, et al. ACGS best practice guidelines for variant classification in rare disease 2020. [https://www.acgs.uk.com/quality/best-practice-guidelines/#VariantGuidelines]
10 Abou Tayoun AN, Pesaran T, DiStefano MT, Oza A, Rehm HL, Biesecker LG, et al.; ClinGen Sequence Variant Interpretation Working Group (ClinGen SVI). Recommendations for interpreting the loss of function PVS1 ACMG/AMP variant criterion. Hum Mutat 2018;39:1517-24.   DOI
11 Jarvik GP, Browning BL. Consideration of cosegregation in the pathogenicity classification of genomic variants. Am J Hum Genet 2016;98:1077-81.   DOI
12 Yorifuji T, Fujimaru R, Hosokawa Y, Tamagawa N, Shiozaki M, Aizu K, et al. Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus. Pediatr Diabetes 2012;13:26-32.   DOI
13 Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.; ACMG Laboratory Quality Assurance Committee. 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.   DOI
14 Johansson BB, Irgens HU, Molnes J, Sztromwasser P, Aukrust I, Juliusson PB, et al. Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry. Diabetologia 2017;60:625-35.   DOI
15 Urakami T. Maturity-onset diabetes of the young (MODY): current perspectives on diagnosis and treatment. Diabetes Metab Syndr Obes 2019;12:1047-56.   DOI
16 Yang YS, Kwak SH, Park KS. Update on monogenic diabetes in Korea. Diabetes Metab J 2020;44:627-39.   DOI
17 Burns C, Bagnall RD, Lam L, Semsarian C, Ingles J. Multiple gene variants in hypertrophic cardiomyopathy in the era of next-generation sequencing. Circ Cardiovasc Genet 2017;10:e001666.   DOI
18 Wang M, Chun J, Genovese G, Knob AU, Benjamin A, Wilkins MS, et al. Contributions of rare gene variants to familial and sporadic FSGS. J Am Soc Nephrol 2019;30:1625-40.   DOI
19 Irgens HU, Molnes J, Johansson BB, Ringdal M, Skrivarhaug T, Undlien DE, et al. Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry. Diabetologia 2013;56:1512-9.   DOI
20 Johnson SR, Ellis JJ, Leo PJ, Anderson LK, Ganti U, Harris JE, et al. Comprehensive genetic screening: the prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort. Pediatr Diabetes 2019;20:57-64.   DOI