ESPE Abstracts (2019) 92 P1-326

Copy Number Variation (CNV) Sequencing Identifies a Novel Mutation of the Glucokinase Gene in Maturity-Onset Diabetes of the Young

Yan Li, Pin Li


Department of Endocrinology, Children's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai, China


Backgrounds: Maturity-onset diabetes of the young (MODY) is a cluster of early-onset, monogenic disorders which is inherited in autosomal dominant form. It is mainly caused by genetic defects in beta-cell, which results in beta-cell dysfunction. Till now, 14 MODY types specified by mutation in respective 14 genes with their etiologies are known. Among them, glucokinase (GCK) gene encodes glucokinase enzyme which plays a crucial role in the regulation of insulin secretion.

Methods: Clinical features and laboratory data were collected from the patient and her family member 10, and linkage analysis and copy number variation (CNV) detection were performed to screen the mutation of all the 14 MDOY gene.

Results: The 3-year-old patient was referred to the endocrinology clinic for evaluation of elevated fasting blood glucose (FBG) measurements. Family studies and laboratory review of other families of hers conformed to the clinical features of MODY. Genetic testing showed the autosomal dominant, deletion mutation in the GCK gene, which is correlated with GCK-MODY. Of the candidate CNV regions, one copy deleted respectively in exon 8, exon 9, exon 10 and exon 11 in all the patients of this family, while normal people have no such deletion mutation, which is a novel mutation of GCK gene.

Conclusion: MODY represents a combination of genetic, metabolic, and clinical heterogenicity. MODY has several subtypes depending upon the involvement of genes and their mutations. Our patients likely represented a novel deletion mutation of GCK-MODY. Besides linkage analysis and exon mutation screening, CNV sequencing might be used to identify other novel GCK mutations.

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