Background: Maturity onset diabetes of the young (MODY) is a group of monogenic disorders classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes.
Methods: In this study, a panel of 23 MODY genes was screened. 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. We clinically evaluated 49 patients and 39 their relatives.
Results: Clinical, laboratory and genetic findings were given in table. At the diagnosis, pubertal status, BMI, BMI-SD, birth weight and fasting c-peptide were significantly different in MODY groups. Mutations were detected in 27 out of 49 patients. 13 patients had GCK mutations. Four new variants were found in five patients: c.1265 G>C, p.Arg422 Pro in exon 10; c.128G>T, p.Arg431 Leu in exon 2; c.532 delG and c.C129Y. Two patients had de novo GCK mutations. Seven patients had BLK gene mutations. Two of them was siblings and they have new mutation in exon 9 (c.900C >A, p.Tyr300Ter). Four patients had known HNF4A mutations in exon 8. Two patients were siblings. Same HNF1A mutation was found in unrelated two patients, and INS gene mutation was identified in one (Table 1).
|At the diagnosis||Glucokinase||BLK||HNF4A||HNF1A||p|
|Fasting c-peptide, ng/mL||0.71±0.4||1.05±0.6||2.04(12)*||4.1±0||0.009|
|G-120 at OGTT, mg/dL (n:25)||164.3±55||124.6±41||220±141||213±49|
|I-0 at OGTT, uIU/mL||2.1(4.81)*||4.3(5.1)*||11.4±4||20.6±14|
|I-120 at OGTT, uIU/mL||26.3±29||28.2±19||36.7±19||20.7±18|
Conclusion: Our study present four novel mutations in GCK, and one novel mutation in BLK gene. Although clinical findings were differing in each MODY group, laboratory results were similar.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology