MODY in Siberia – molecular genetics and clinical characteristics

Ovsyannikova, Alla; Rymar, O. D.; Shakhtshneider, E.; Воропаева, Е. Н.; Ivanoshchuk, D.; Voevoda, Mikhail

doi:10.14341/dm7920

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…Moreover, when examining Iranian families with diabetes, Sarmadi et al ( 20 ) concluded that the CEL variant p.Ile488Thr causes MODY, even if present at an allele frequency of 0.01 in various Middle Eastern populations. Other single cases or families proposed to carry pathogenic CEL mutations outside the VNTR have been published from India ( 21 ), Siberia ( 22 ), China ( 23 ), and South Korea ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases

Jellas

Dušátková

Haldorsen

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Objective Maturity-onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. To facilitate correct MODY8 diagnostics, we screened two cohorts of diabetes patients and delineated the phenotype. Research design Young, lean Swedish and Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases who had tested negative for common MODY genes. For CEL mutation-positive subjects, family history was recorded, and clinical investigations and pancreatic imaging performed. Results One Swedish and one Czech case with germline mutation in CEL were identified. Clinical and radiological investigations of these two probands and their families revealed dominantly inherited insulin-dependent diabetes, pancreatic exocrine dysfunction and atrophic pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the predominant phenotype in one pedigree. Both families carried single-base pair deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) region in exon 11. The mutations are predicted to lead to aberrant protein tails that make the CEL protein susceptible to aggregation. Conclusions The diagnosis of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR in addition to dominantly inherited diabetes. CEL screening may be warranted also in families with hereditary pancreatitis of unknown genetic etiology.

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Section: Discussionmentioning

confidence: 99%

Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases

Jellas

Dušátková

Haldorsen

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review

Aarthy

Aston-Mourney

Mikocka‐Walus

et al. 2021

Journal of Diabetes and its Complications

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GCK-MODY diabetes course in persons over 18 years of age: prospective observation

Ovsyannikova

Shakhtshneider

Ivanoshchuk³

et al. 2021

Diabetes mellitus

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Most young patients with hyperglycemia have type 1 diabetes and type 2 diabetes but up to 10% of all cases of the disease occur in MODY (Maturity Onset Diabetes of the Young). Published abstracts show features of the debut, laboratory and genetic characteristics of MODY in the Russian population. However there is a small amount of data on the clinical course of this nosology in the Russian Federation.Aim: To investigate the characteristics of the 3-year course of GCK-MODY diagnosed after 18 years.Materials and methods: 85 probands and 46 relatives of the first and second degrees of kinship with a clinical diagnosis of GCK-MODY were examined: biochemical and hormonal blood tests, ultrasound, molecular genetic studies. Patients were invited for a follow-up visit 3 years after verification of the pathogenic mutations associated with GCK-MODY. Examination, biochemical and hormonalanalyzes , ultrasound were done in second visit.Results: The diagnosis GCK-MODY was verified by a molecular genetic study in 25 probands (29.4%). In 33 of 46 (71.7%) relatives of patients with GCK-MODY were diagnosed identical mutations. In 31 patients with GCK-MODY diagnosed after 18 years, a dynamic observation was performed for three years. Most patients over 18 years of age did not have clinical manifestations of carbohydrate metabolism disorders when diagnosing GCK-MODY and follow up visit. Skin rashes and allergic reactions prevailed among concomitant pathologies. Patients with GCK-MODY had preserved β-cell secretion, HbA1c targets were achieved. Low fasting hyperglycemia prevailed which persisted even after treatment correction. Among the characteristics of carbohydrate metabolism, biochemical, lipid and hormonal parameters during GCK-MODY verification and after three years of observation no significant differences were obtained, which indicates a stable course of the disease. Half of the patients achieved normoglycemia by rational nutrition, two people with GCK-MODY within three years after determining the diagnosis were transferred from insulin therapy to oral glucose-lowering drugs. Among oral glucose-lowering drugs prior to GCK-MODY verification most patients used metformin, 3 years later — dipeptidyl peptidase-4 inhibitors.Conclusion. The results of a three-year follow-up of a group of patients with GCK-MODY demonstrate a non-progressive course of this type of diabetes with stable indicators of carbohydrate metabolism and low fasting hyperglycemia that persists after 3 years of observation. With the verification of GCK-MODY and the achievement of the target values of glycated hemoglobin and postprandial glycaemia by rational nutrition, even if a low level of fasting hyperglycemia is determined, the prescription of oral glucose-lowering drugs is not indicated in most cases.

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MODY in Siberia – molecular genetics and clinical characteristics

Cited by 3 publications

References 19 publications

Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases

Two New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Cases

Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review

GCK-MODY diabetes course in persons over 18 years of age: prospective observation

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