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- Title
TWO OPPOSITE PHENOTYPES OF GLUCOSE DISORDERS IN A FAMILY WITH HETEROZYGOUS P.SER453LEU (C.1358C> T) MUTATION IN THE GLUCOKINASE (GCK) GENE: MATURITY ONSET DIABETES IN YOUNG AND INSULINOMA.
- Authors
Demiral, M.; Çelebi, H. B. G.; Cander, S.; Yerci, O.; Eren, E.; Demirbilek, H.
- Abstract
Background. Heterozygous gain-of-function mutations in the glucokinase (GCK) gene cause hyperinsulinaemic hypoglycaemia (GCK-HI), while loss- of-function mutations lead to a monogenic type of diabetes (GCK-MODY). We, herein, report a heterozygous GCK gene mutation in a large family with GCK-MODY and insulinoma in one individual from the same family. Patients and methods. The proband, an 11-year- old male, was referred for asymptomatic mild hyperglycemia (fasting glucose:121 mg/dL) and HbA1c of 6.1%. Segregation analysis of the family revealed multiplex members with asymptomatic fasting hyperglycaemia or non-insulin- dependent diabetes and 33-year-old maternal uncle of the proband case had a history of distal pancreatectomy due to the diagnosis of insulinoma. His preoperative investigations were revealed fasting glucose of 31 mg/dL, insulin: 7μU/ mL, C-peptide: 2.6 mg/dL, and a low HbA1c(4.0%) which was suggestive for recurring hypoglycaemia episodes. Post- pancreatectomy he developed mild fasting hyperglycemia (115-136 mg/dL). Results. Genetic analysis revealed heterozygous p.Ser453Leu(c.1358C> T) mutation in the GCK gene in the proband. In segregation analysis, the identical heterozygous p.Ser453Leu(c.1358C> T) GCK gene mutation was detected in all of the other affected family members for whom a DNA analysis was applicable. The maternal uncle was first diagnosed with insulinoma and underwent a pancreatectomy. He also had an identical mutation in a heterozygous state. Conclusion. We, to the best of our knowledge, firstly identified these two entirely distinct phenotypes of glucose metabolism, GCK-MODY and GCK-HI, due to an identical heterozygous p.Ser453Leu (c.1358C> T) mutation in the GCK. Further studies required to elucidate this new phenomenon and understanding the genotype-phenotype relationship of GCK gene mutations.
- Subjects
MATURITY onset diabetes of the young; INSULINOMA; TYPE 2 diabetes; GLUCOKINASE; PHENOTYPES; GAIN-of-function mutations; DNA analysis
- Publication
Acta Endocrinologica (1841-0987), 2022, Vol 18, Issue 4, p458
- ISSN
1841-0987
- Publication type
Article
- DOI
10.4183/aeb.2022.458