MODY genetics: novel variants and genotype-phenotype correlation

Çankaya T., Bozkurt S., Ataseven Kulalı M., Koç A., Böber E., Abacı A., ...Daha Fazla

5. Erciyes Uluslararası Katılımlı Genetik Günleri Kongresi, Nevşehir, Türkiye, 20 - 22 Şubat 2020, cilt.31, sa.3, ss.79

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 31
  • Basıldığı Şehir: Nevşehir
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.79
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Maturity onset diabetes of the young (MODY) is an autosomal dominant inherited, most common subtype of the

monogenic diabetes and responsible for 1-3% of all cases of diabetes. MODY is frequently misdiagnosed because of

confused with Type 1 and Type 2 DM. To improve the prognosis of MODY, it is important to identify the affected subjects

as early as possible.

Known MODY-related genes can be identified by next-generation sequencing method to predict the clinical

disease course and offer the most appropriate treatment. In this sense, candidates for genetic testing may include

positive family history of diabetes, nonobese subjects with hyperglycemia, no insulin requirements. Genetic

heterogeneity exists, at least 14 genes have been reported. Mutations in GCK and HNF1A genes are the most frequently

identified etiologies that account for 30-60% of the MODY while HNF4A and HNF1B gene mutations are responsible for

approximately 10% of all affected patients in the world.

Since some MODY subtypes are associated with additional manifestations, clinical symptoms may help to identify the

disease causing MODY genes. For instance, HNF1B mutations are associated with developmental disorders of the kidney,

renal cysts, hyperuricemia, hypomagnesemia, and early-onset gout or HNF4A mutations associated with the case of

macrosomia and congenital hypoglycemia.

In this retrospective study, we analyzed samples that had been obtained from a total of 74 patients with MODY by

custom design next generation sequencing panel which includes GCK, HNF1A, HNF1B, HNF4A, PDX1, NEUROD1, KLF11,

CEL, PAX4, BLK and INS genes.

Pathogenic and likely pathogenic variants were found in 19 (25%) patients. Of these, six mutations (5 missenses and a

nonsense mutation) were novel. Similar with the literature, GCK mutations were the most common cause of MODY in

our study population. Disease causing variants were confirmed and segregation analysis were performed with Sanger

sequencing. Genetic counseling was given.

In this study, new variants have been added to the mutation spectrum in MODY genes and genotype-phenotype

correlations have been studied.