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Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing

  • Ahmet Anık EMAIL logo , Gönül Çatlı , Ayhan Abacı , Erkan Sarı , Ediz Yeşilkaya , Hüseyin Anıl Korkmaz , Korcan Demir , Ayça Altıncık , Hale Ünver Tuhan , Sefa Kızıldağ , Behzat Özkan , Serdar Ceylaner and Ece Böber
Published/Copyright: July 30, 2015
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 11-12

Abstract

Aim: To perform molecular analysis of pediatric maturity onset diabetes of the young (MODY) patients by next-generation sequencing, which enables simultaneous analysis of multiple genes in a single test, to determine the genetic etiology of a group of Turkish children clinically diagnosed as MODY, and to assess genotype-phenotype relationship.

Methods: Forty-two children diagnosed with MODY and their parents were enrolled in the study. Clinical and laboratory characteristics of the patients at the time of diagnosis were obtained from hospital records. Molecular analyses of GCK, HNF1A, HNF4A, HNF1B, PDX1, NEUROD1, KLF11, CEL, PAX4, INS, and BLK genes were performed on genomic DNA by using next-generation sequencing. Pathogenicity for novel mutations was assessed by bioinformatics prediction software programs and segregation analyses.

Results: A mutation in MODY genes was identified in 12 (29%) of the cases. GCK mutations were detected in eight cases, and HNF1B, HNF1A, PDX1, and BLK mutations in the others. We identified five novel missense mutations – three in GCK (p.Val338Met, p.Cys252Ser, and p.Val86Ala), one in HNF1A (p.Cys241Ter), and one in PDX1 (p.Gly55Asp), which we believe to be pathogenic.

Conclusion: The results of this study showed that mutations in the GCK gene are the leading cause of MODY in our population. Moreover, genetic diagnosis could be made in 29% of Turkish patients, and five novel mutations were identified.

Keywords: childhood; MODY; next-generation sequencing
Corresponding author: Ahmet Anık, MD, Faculty of Medicine, Department of Pediatric Endocrinology, Dokuz Eylul University, 35340, Balçova, İzmir, Turkey, Phone: +90-232-4126081, Fax: +90-232-4126001, E-mail:

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Received: 2014-10-13
Accepted: 2015-6-22
Published Online: 2015-7-30
Published in Print: 2015-11-1

©2015 by De Gruyter

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https://doi.org/10.1515/jpem-2014-0430
Keywords for this article
childhood; MODY; next-generation sequencing

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Turner syndrome
  3. Turner syndrome – working together with patients and their families
  4. Turner syndrome patients with bicuspid aortic valves and renal malformations exhibit abnormal expression of X-linked inhibitor of apoptosis protein (XIAP)
  5. Inhibin B in adolescents and young adults with Turner syndrome
  6. Mode of initial presentation and chromosomal abnormalities in Irish patients with Turner syndrome: a single-centre experience
  7. Retrospective evaluation of pubertal development and linear growth of girls with Turner Syndrome treated with oral and transdermal estrogen
  8. Turner syndrome in Albania and the efficacy of its treatment with growth hormone
  9. Review articles
  10. The relation of vitamin D status with metabolic syndrome in childhood and adolescence: an update
  11. Putting the pieces together: cryptorchidism – do we know everything?
  12. Original articles
  13. Investigation of androgen receptor gene mutations in a series of 21 patients with 46,XY disorders of sex development
  14. Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing
  15. Association of physical activity level with depression, anxiety, and quality of life in children with type 1 diabetes mellitus
  16. Neonatal diabetes in Ukraine: incidence, genetics, clinical phenotype and treatment
  17. The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children
  18. Are obesity and metabolic syndrome associated with plasma adropin levels in children?
  19. Carnitine insufficiency in children with inborn errors of metabolism: prevalence and treatment efficacy
  20. Comparison of energy expenditure, body composition, metabolic disorders, and energy intake between obese children with a history of craniopharyngioma and children with multifactorial obesity
  21. Effect of serum cholesterol on bone mineral density in normal-weight children and adolescents
  22. Assessment of bone turnover markers and bone mineral density in normal short boys
  23. Long-term treatment for hyperphenylalaninemia and phenylketonuria: a risk for nutritional vitamin B12 deficiency?
  24. Risk factors affecting the development of nephrocalcinosis, the most common complication of hypophosphatemic rickets
  25. Children with hyperthyroidism younger than age 7 require higher mg/kg doses of methimazole to normalize free T4 compared to older children
  26. Effects of bisphosphonates to treat osteoporosis in children with cerebral palsy: a meta-analysis
  27. AMH levels at central precocious puberty and premature thelarche: is it a parameter?
  28. Validating Paediatric Morphometrics: body proportion measurement using photogrammetric anthropometry
  29. Treatment of central precocious puberty and early puberty with GnRH analog in girls with Williams-Beuren syndrome
  30. Short communication
  31. Pilot study on the dietary habits and lifestyles of girls with idiopathic precocious puberty from the city of Rome: potential impact of exposure to flame retardant polybrominated diphenyl ethers
  32. Patient reports
  33. Hypomagnesemia due to two novel TRPM6 mutations
  34. A novel mutation of AMH in three siblings with persistent Mullerian duct syndrome
  35. Kocher-Debré-Semelaigne syndrome with rhabdomyolysis and increased creatinine
  36. Anaphylaxis to gonadorelin acetate in a girl with central precocious puberty
  37. Efficacy and safety of sirolimus in a neonate with persistent hypoglycaemia following near-total pancreatectomy for hyperinsulinaemic hypoglycaemia
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