ESPE Abstracts (2014) 82 P-D-1-2-79

ESPE2014 Poster Presentations Diabetes (1) (12 abstracts)

Sequence Analysis of 11 Known Causative Genes in Clinically Diagnosed Children as Maturity Onset Diabetes of Youth by Next Generation Sequencing

Sebahat Yilmaz Agladioglu a , Zehra Aycan a , Semra Cetinkaya a , Veysel Nijat Bas a , Asan Onder a , Havva Nur Peltek Kendirci a , Haldun Dogan b & Serdar Ceylaner a

aDr Sami Ulus Children’s Health and Disease Training and Research Hospital Clinics of Pediatric Endocrinology, Ankara, Turkey; bIntergen Genetic Centre, Ankara, Turkey

Introduction: Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseases in the pancreatic β–cell that impair insulin secreation. It mostly caused by heterozygous mutations in one of 11 different genes associated with β–cell function. The aim of this study is detection of the distribution of both known and novel point mutations of these genes in Turkish population.

Patients and method: This study includes patients diagnosed as MODY by clinical criterias. 43 children was included this study. Primers were designed for all coding regions and intron–exon boundaries for 11 known genes given in Online Mendelian Inheritance in Man Database (OMIM) (HNF4A, GCK, HNF1A, PDX 1, TCF2, NEUROD1, KLF11, CEL, PAX4, INS, BLK).

Results: Twenty-six of patients were males (61%) and 17 were (39%) females. Family history of 29 patients (67.4%) presents typical three generation diabetes. Thirty six of them (83.7%) has an affected parent. Ages of diagnosis were within 1-20 years (10.1±4.5). Mean of diabetes ages were calculated as 2.46±2.01. Thirty-four out of 43 patients (79%) have point mutations. Eighteen patients have GCK mutations (53%), six have (17%) KLF11, four have (12%) HNF1A, two have (6%) NEUROD1, one has (3%) HNF1B, one has (3%) HNF4A, one has (3%) PDX1 gene variations. One patient has (3%) both HNF1A and HNF4A heterozygote mutations. Clinical features, mutations, numbers of patients were summarized. Twenty different mutations were detected in 34 patients. Eleven of them are proven and previously reported mutations while 15 patients have novel highly likely pathogenic mutations (44%).

Conclusions: The most common types in our group is MODY 2. The known mutations are not found in 55% of our patients. This situation have been interpreted as evidence known mutations do not compose all the patients, and MODY distribution vary between communities.

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