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. 2021 Aug 5:12:700342.
doi: 10.3389/fendo.2021.700342. eCollection 2021.

Precision Therapy for a Chinese Family With Maturity-Onset Diabetes of the Young

Juyi Li  1 , Meng Shu  2 , Xiufang Wang  3 , Aiping Deng  1 , Chong Wen  4 , Juanjuan Wang  5 , Si Jin  2 , Hongmei Zhang  5
Affiliations

Precision Therapy for a Chinese Family With Maturity-Onset Diabetes of the Young

Juyi Li et al. Front Endocrinol (Lausanne). .

Abstract

Objective: To determine the pathogenic gene and explore the clinical characteristics of maturity-onset diabetes of the young type 2 (MODY2) pedigree caused by a mutation in the glucokinase (GCK) gene.

Methods: Using whole-exome sequencing (WES), the pathogenic gene was detected in the proband-a 20-year-old young man who was accidentally found with hyperglycemia, no ketosis tendency, and a family history of diabetes. The family members of the proband were examined. In addition, relevant clinical data were obtained and genomic DNA from peripheral blood was obtained. Pathologic variants of the candidate were verified by Sanger sequencing technology, and cosegregation tests were conducted among other family members and non-related healthy controls. After adjusting the treatment plan based on the results of genetic testing, changes in biochemical parameters, such as blood glucose levels and HAblc levels were determined.

Results: In the GCK gene (NM_000162) in exon 9, a heterozygous missense mutation c.1160C > T (p.Ala387Val) was found in the proband, his father, uncle, and grandmother. Thus mutation, which was found to co-segregate with diabetes, was the first discovery of such a mutation in the Asian population. After stopping hypoglycemic drug treatment, good glycemic control was achieved with diet and exercise therapy.

Conclusion: GCK gene mutation c.1160C > T (p.Ala387Val) is the pathogenic gene in the GCK-MODY pedigree. Formulating an optimized and personalized treatment strategy can reduce unnecessary excessive medical treatment and adverse drug reactions, and maintain a good HbA1c compliance rate.

Keywords: MODY2; glucokinase; monogenic diabetes; mutation; pedigree.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with the authors at time of review.

Figures

Figure 1
Figure 1
The family pedigree. Squares represent males, circles represent females. The proband is represented by a solid black box, and the red line indicates patients with diabetes. The proband (III-1), his father (II-2), his uncle (II-3), and his grandmother (I-2) were diagnosed with type 2 diabetes (T2D) at the age of 18, 42, 43, and 60, respectively.
Figure 2
Figure 2
A mutation in the GCK gene causes MODY2. (A): GCK wild type; (B): GCK heterozygote.
Figure 3
Figure 3
Predicted computational tertiary structure. The wild genotype is presented on the left; the mutant genotype is presented on the right.
See this image and copyright information in PMC

References

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