부산대학교 도서관

INTRODUCTION Maturity onset diabetes of the youth (MODY), which is estimated to account for 1-2% of all patients with diabetes, is a monogenic form of diabetes that is inherited in [...]
Objective: Maturity-onset diabetes of the youth (MODY) is a genetically and clinically heterogeneous group of diseases which is often misdiagnosed as type 1 diabetes or type 2 diabetes. The aim of this study is to identify the occurence of mutations in subjects classified clinically as having MODY, and to determine phenotypic features and their long-term monitering consequences. Methods: Eighteen probands were selected based on the clinical criteria of MODY. Firstly, in patients with mild stable fasting hyperglycemia who did not progress, Sanger sequencing of GCK gene was performed as GCK-MODY was the most common cause of persistent and incidental hyperglycemia in the pediatric population. Patients without a GCK gene mutation or without mild fasting hyperglycemia were analysed by using targeted next-generation sequence for seven known monogenic genes of diabetes (ABCC8, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11) to identify the molecular pathology. Results: We identified 11 GCK, 2 HNF1A, 2 KCNJ11 mutations in 18 probands. Eleven of them (73%) were previously reported and 4 of them (27%) were assessed as novel mutations. In two patients who were treated with insulin before the molecular analysis, insulin was switched to sulfonylurea and glibenclamide, after determination of pathogenic variants in HNF1A and KCNJ11, respectively. Retinopathy or nephropathy was not detected among the patients. Conclusion: The MODY has a large spectrum of clinical presentations. We detected 4 novel mutations among our cohort. Although GCK-MODY was the most frequent type of our study population, identification of rare MODY types and follow-up of these patients would help us better understand monogenic diabetes. Keywords: Diabetes, MODY, next-generation sequencing Amac: Genclerin eriskin tipi diyabeti (Maturity onset diabetes of young - MODY), genellikle tip 1 diyabet veya tip 2 diyabet olarak yanlis teshis edilebilen, genetik ve klinik olarak heterojen bir hastalik grubudur. Bu calismanin amaci, klinik olarak MODY olarak siniflandirilan olgularda mutasyonlarini, fenotipik ozelliklerini tespit etmek ve bunlarin uzun vadeli izlem sonuclarini gostermektir. Yontemler: MODY klinik kriterlerine gore 18 olgu secildi. Ilk olarak, pediatrik populasyonda kalici, tesadufi hipergliseminin en yaygin nedeni GCKMODY oldugundan, ilerleyici olmayan, hafif stabil aclik hiperglisemisi olan hastalarda, GCK geninin Sanger dizilemesi yapildi. GCK gen mutasyonu olmayan veya hafif aclik hiperglisemisi olmayan hastalar, molekuler patolojiyi belirlemek icin bilinen yedi monogenik diyabet geni (ABCC8, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11) icin hedeflenen yeni nesil diziyle analiz edildi. Bulgular: On sekiz probandda 11 GCK, 2 HNF1A, 2 KNCJ11 mutasyonu belirledik. Bunlarin 11'i (%73) daha once tespit edilmis ve 4'u (%27) yeni mutasyonlar olarak degerlendirilmistir. Molekuler analizden once insulin ile tedavi edilen iki hastada, sirasiyla HNF1A ve KCNJ11'de patojenik varyantlarin belirlenmesinden sonra tedaviler sulfonilure ve glibenklamid olarak degistirildi. Hastalar arasinda retinopati veya nefropati saptanmadi. Sonuc: MODY, genis bir klinik sunum yelpazesine sahiptir. Kohortumuzda 4 yeni mutasyon tespit ettik. GCK-MODY calisma populasyonumuzda en sik gorulen tip olmasina ragmen, nadir MODY tiplerinin belirlenmesi ve bu hastalarin takibi monogenik diyabeti daha iyi anlamamiza yardimci olacaktir. Anahtar kelimeler: Diyabet, MODY, yeni nesil dizileme