ESPE Abstracts (2018) 89 P-P1-056

Different Clinical Findings in Maturity Onset Diabetes of the Young due to B-Lymphocyte Kinase Gene Mutations

Ayla Güvena & Canan Yildirimoglub

aSaglik Bilimleri University, Zeynep Kamil Maternity and Children Hospital, Pediatric Endocrinology Clinic, İstanbul, Turkey; bSaglik Bilimleri University, Ankara Numune Hospital, Center of Genetic Diagnosis, Ankara, Turkey

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 it’s 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.

Table 1
No, SexCase 1, FCase 2, MCase 3, MCase 4, FCase 5, FCase 6, MCase 7, M
Age at diagnosis, years15.413.0812.0811.7274.245.88
Birth weight, gr2850340029003200NA27303730
Affected parentsFatherMother
Gestational DM in motherNoNoUnknownYesNoYesYes
BMI, kg/m220.6915.5221.0515.7318.0616.2821.10
Fasting Glucose mg/dL77104279141157112130
2 hr-Glucose, mg/dL68173Not performed166137102102
Fasting insulin, uIU/mL11.
Fasting c-peptide, ng/mL1.60.880.09NA1.570.681.48
c.DNAc.1075 C>Tc.211G>Ac.211G>Ac.211G>Ac.223C>Gc.900C >Ac.900C >A
A.acid changep.Arg359Cysp.Ala71Thrp.Ala71Thrp.Ala71Thrp.Arg75Glyp.Tyr300Terp.Tyr300Ter
ACGM 2015 guidelineUncertain significanceLikely BenignLikely BenignLikely BenignUncertain significanceNovelNovel

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.

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