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      MODY2 in Asia: analysis of GCK mutations and clinical characteristics

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          Abstract

          Aims

          Heterozygous inactivating mutations in the GCK gene cause the familial, mild fasting hyperglycaemia named MODY2. Many patients with MODY2 in Asia have delayed timely treatment because they did not receive the correct diagnosis. This study aims to analyze the clinical characteristics and GCK mutations in Asian MODY2.

          Methods

          We have collected 110 Asian patients with MODY2 from the PubMed, Embase, Medline, Web of Science, CNKI, and Wanfang with the following search terms: ‘maturity-onset diabetes of the young’ OR ‘MODY’ OR ‘maturity-onset diabetes of the young type 2’ OR ‘MODY2’ OR ‘GCK-DM’ OR ‘GCK-MODY’. Both mutations of GCK and clinical characteristics of MODY2 were analyzed.

          Results

          There were 96 different mutations that occurred in coding regions and non-coding regions. Exon 5 and 7 were the most common location in coding regions and missense was the primary mutation type. The proportion of probands younger than 25 was 81.8%, and 81.4% of the probands had family history of hyperglycaemia. Ninety percent and 93% of Asian MODY2 probands exhibited mild elevation in FPG (5.4–8.3 mmol/L) and HbA1c (5.6–7.6%), respectively.

          Conclusions

          In most Asian patients, MODY2 occurred due to GCK mutation in coding regions, and exon 5 and 7 were the most common locations. FPG, HbA1c, and familial diabetes were important reference indicators for diagnosing MODY2. Altogether, the study indicates that for the young onset of diabetes with mild elevated blood glucose and HbA1c and family history of hyperglycaemia, molecular genetic testing is suggested in order to differentiate MODY2 from other types of diabetes earlier.

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          Most cited references42

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          Maturity-onset diabetes of the young (MODY): how many cases are we missing?

          Maturity-onset diabetes of the young is frequently misdiagnosed as type 1 or type 2 diabetes. A correct diagnosis of MODY is important for determining treatment, but can only be confirmed by molecular genetic testing. We aimed to compare the regional distribution of confirmed MODY cases in the UK and to estimate the minimum prevalence. UK referrals for genetic testing in 2,072 probands and 1,280 relatives between 1996 and 2009 were examined by region, country and test result. Referral rate and prevalence were calculated using UK Census 2001 figures. MODY was confirmed in 1,177 (35%) patients, with HNF1A (52%) and GCK mutations (32%) being most frequent in probands confirmed with MODY. There was considerable regional variation in proband referral rates (from 50 per million for South West England and Scotland) and patients diagnosed with MODY (5.3 per million in Northern Ireland, 48.9 per million in South West England). Referral rates and confirmed cases were highly correlated (r = 0.96, p 80% of MODY is not diagnosed by molecular testing. The marked regional variation in the prevalence of confirmed MODY directly results from differences in referral rates. This could reflect variation in awareness of MODY or unequal access to genetic testing. Increased referral for diagnostic testing is required if the majority of MODY patients are to have the genetic diagnosis necessary for optimal treatment.
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            Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus.

            Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM.
              • Record: found
              • Abstract: not found
              • Article: not found

              ISPAD Clinical Practice Consensus Guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                May 2020
                06 May 2020
                : 9
                : 5
                : 471-478
                Affiliations
                [1 ]Department of Endocrinology and Metabology , The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
                [2 ]Laboratory of Endocrinology , Medical Research Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Ji-nan, China
                [3 ]Department of Endocrinology , Qilu Hospital of Shandong University, Ji-nan, China
                [4 ]Department of Endocrinology and Metabology , Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Ji-nan, China
                Author notes
                Correspondence should be addressed to J Dong or L Liao: cwc_ll@ 123456sdu.edu.cn or liaolin@ 123456sdu.edu.cn
                Article
                EC-20-0074
                10.1530/EC-20-0074
                7274558
                32375122
                9ea7fb6f-85e3-4e98-854d-454828af5014
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 22 April 2020
                : 06 May 2020
                Categories
                Research

                mody2,gck,asian,characteristics
                mody2, gck, asian, characteristics

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