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Two novel GCK mutations in Chinese patients with maturity-onset diabetes of the young

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Abstract

Purpose

Heterozygous inactivating mutations in the glucokinase (GCK) gene result in the asymptomatic fasting hyperglycemia named as GCK-MODY or MODY2. The genetic testing can effectively avoid the misdiagnosis and inappropriate treatment for GCK-MODY.

Methods

A total of 25 unrelated families with MODY were screened for mutations in coding region of GCK by using direct sequencing. Three different bioinformatics tools such as PolyPhen2, Mutation Taster and PROVEAN were performed to predict the function of mutant proteins. The glucose profile was recorded by continuous glucose monitoring system (CGMS) to evaluate the glycemic variability for the GCK-MODY patient.

Results

Our study identified five GCK mutations in 24% of the families (6/25): two novel mutations (I126fs and G385A) and three already described mutations (G44S, H50fs and S383L). In silico analyses predicted that these mutations altered structural conformational changes. The values of mean amplitude of glycemic excursions (MAGE), an important index of blood glucose fluctuation in CGMS system, were 0.81 in the first 24 h and 1.61 in the second 24 h record in the patient with GCK-MODY (F3), suggesting little glucose fluctuation.

Conclusion

The genetic testing is suggested to be important to differentiate GCK-MODY from other types of diabetes. CGMS might be used to screen GCK-MODY cases prior to genetic testing.

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Acknowledgements

This study was supported by grants from Jiangsu Provincial Double-Innovation Doctor Program and Gusu health personnel program. We thank the patient and their family members in this study and gratefully acknowledge the skillful technical support of all the nursing and medical staff at department of endocrinology in the Second Affiliated Hospital of Soochow University. We also thank the Shanghai Diabetes Institute and School of Biological & Basic Medicine Sciences of Soochow University for support of genetic sequencing.

Author contributions

C.F. and J.H. contributed to the study conception and design. Material preparation, data collection and analysis were performed by M.Z. and Y.W. The first draft of the manuscript was written by T.W. and all authors commented on previous versions of the manuscript. We also thank C.H. from the Shanghai Diabetes Institute for support of genetic sequencing. All authors read and approved the final manuscript.

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Author notes

  1. These authors contributed equally: Tao Wang, Mengmeng Zhu

Authors and Affiliations

  1. Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Tao Wang, Mengmeng Zhu, Chen Fang & Ji Hu

  2. Department of Clinical Laboratory, Suzhou Guangji Hospital, Suzhou, 215123, China

    Yun Wang

  3. Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

    Cheng Hu

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  1. Tao Wang
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Correspondence to Chen Fang or Ji Hu.

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All procedures performed in studies involving human participants were in accordance with the ethic committee of the Second Affiliated Hospital of Soochow University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Wang, T., Zhu, M., Wang, Y. et al. Two novel GCK mutations in Chinese patients with maturity-onset diabetes of the young. Endocrine 83, 92–98 (2024). https://doi.org/10.1007/s12020-023-03509-1

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