Background: B-Lymphocyte kinase gene (BLK) gene acts on insulin synthesis and secretion, and mapped locus on chromosome 8p23. Monogenic diabetes due to BLK gene mutation is very rare and its named as MODY11. We aimed to present differences in clinical, laboratory and treatment of the patients with BLK mutations.
Methods: OGTT performed in six patients. A panel of 23 MODY genes was screened. Patients with BLK mutations seperated. The Human Gene Mutation Database (HGMD), Clinvar, dbSNP and Exac database used for known or new variants causes MODY. Classification of variants performed according to ACMG 2015 Guidelines.
Results: Case 1 had recurrent hypoglycemic attacts. However her grandmother and maternal uncle have diabetes. Six patients had hyperglycemia and diabetes symptoms such as polyuria and polydypsia. Case 6 and 7 were siblings and their parents were first cousin. Seven patients have heterozygous mutation in BLK gene. Clinical, laboratory and genetic results of the patients were given in Table 1. Mutations in siblings were novel. Although basal and bolus insulin therapy for Case 3 and metformin therapy for Case 4 were given, diet was enough to regulate blood glucose.
|No, Sex||Case 1, F||Case 2, M||Case 3, M||Case 4, F||Case 5, F||Case 6, M||Case 7, M|
|Age at diagnosis, years||15.4||13.08||12.08||11.72||7||4.24||5.88|
|Birth weight, gr||2850||3400||2900||3200||NA||2730||3730|
|Gestational DM in mother||No||No||Unknown||Yes||No||Yes||Yes|
|Fasting Glucose mg/dL||77||104||279||141||157||112||130|
|2 hr-Glucose, mg/dL||68||173||Not performed||166||137||102||102|
|Fasting insulin, uIU/mL||11.5||8.9||3.6||4.1||5.09||3.8||4.3|
|Fasting c-peptide, ng/mL||1.6||0.88||0.09||NA||1.57||0.68||1.48|
|c.DNA||c.1075 C>T||c.211G>A||c.211G>A||c.211G>A||c.223C>G||c.900C >A||c.900C >A|
|ACGM 2015 guideline||Uncertain significance||Likely Benign||Likely Benign||Likely Benign||Uncertain significance||Novel||Novel|
Conclusion: We found one novel mutation in BLK gene. Also two uncertain significances in BLK gene were presented. More patient information is needed to identify patients referral findings and treatment modalities.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology