Öz
Amaç
Bu çalışmanın amacı gençlerde başlayan erişkin tipi diyabet (MODY) şüphesi ile genetik analiz yapılan hastaların özelliklerini değerlendirmektir.
Yöntemler
Ölçülebilir serum açlık C-peptid düzeyleri, pozitif aile öyküsü, otoantikor negatifliği gibi kriterlere uyan ve genç yaşta diyabet tanısı alan 40 hastanın demografik, klinik, laboratuvar ve moleküler test sonuçları incelendi. Tamamı yeni nesil dizileme yöntemi ile 30 hastada (%75), 21 genin [hepatosit nükleer faktör 4 alfa (HNF4A), glukokinaz (GCK), HNF 1 alfa (HNF1A), pankreatik ve duodenal homeobox 1, HNF 1 beta (HNF1B), nörojenik farklılaşma 1, kruppel benzeri faktör 11, karboksil ester lipaz, paired box proteini 4, insülin, B lenfoid tirozin kinaz, adenozin trifosfat bağlı kompaktörü subfamilisi C üyesi 8, potasyum inwardly rectifying kanal subfamiliyası J üyesi 11, AKT2, GLIS ailesi çinko parmak proteini 3, glutamat dehidrogenaz 1, hidroksi asil‑koa dehidrogenaz , insülin reseptörü, sitozol membran taşıyıcı 2 , wolfram sendrom 1 proteini, çinko parmağı proteini 57] incelendiği kapsamlı MODY paneli ve 10 hastada (%25) GCK, HNF1A, HNF1B ve HNF4A genlerini içeren kısa panel kullanılarak saptanan varyantlar, farklı veri tabanları (insanlarda çevrim içi mendel kalıtımı veritabanı, tek nükleotid polimorfizmi veritabanı, genom toplulaştırma veritabanı, insan gen mutasyonları veritabanı) kullanılarak analiz edildi.
Bulgular
Tüm hastalar içinde 10 hastada (%25) toplam 7 ayrı gende, 11 varyant tespit edildi. Mutasyon pozitif hastaların %60’ı (n=6) insülin kullanmaktaydı. Mutasyon pozitif ve negatif gruplar arasındaki serum açlık C-peptid düzeyleri (1,18’e 1,26 ng/mL, p=0,891) ve diyabet tanısı aldıkları yaşlar (26,5’e 29,0 yıl, p=0,860) arasında fark yoktu.
Sonuç
Gelişen tanı imkânlarına rağmen MODY hastaları hala gözden kaçmakta ve önemli bir kısmı gereksiz yere insülin ile tedavi edilmektedir. Özellikle genç yaşta diyabet tanısı alan, otoantikorları negatif, ölçülebilir serum C-peptid düzeyleri olan hastalar, MODY açısından gözden geçirilmelidir.
Anahtar Kelimeler: MODY, yeni nesil dizi analizi, GCK, HNF1A, HNF4A
Kaynakça
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