open access

Vol 70, No 1 (2019)
Original papers
Published online: 2018-09-21
Submitted: 2018-03-15
Accepted: 2018-07-11
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The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young

Jovana Komazec, Vera Zdravkovic, Silvija Sajic, Maja Jesic, Marina Andjelkovic, Sonja Pavlovic, Milena Ugrin
DOI: 10.5603/EP.a2018.0064
·
Pubmed: 30259503
·
Endokrynologia Polska 2019;70(1):28-36.

open access

Vol 70, No 1 (2019)
Original papers
Published online: 2018-09-21
Submitted: 2018-03-15
Accepted: 2018-07-11

Abstract

Introduction: Maturity onset diabetes of the young (MODY) is a rare form of monogenic diabetes. Being clinically and genetically heterogeneous, it is often misdiagnosed as type 1 or type 2 diabetes, leading to inappropriate therapy. MODY is caused by a single gene mutation. Thirteen genes, defining 13 subtypes, have been identified to cause MODY. A correct diagnosis is important for the right therapy, prognosis, and genetic counselling.
Material and methods: Twenty-nine unrelated paediatric patients clinically suspected of having MODY diabetes were analysed using TruSight One panel for next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) assay.
Results: In this study we identified variants in MODY genes in 22 out of 29 patients (75.9%). Using two genetic tests, NGS and MLPA, we detected both single nucleotide variants and large deletions in patients. Most of the patients harboured a variant in the GCK gene (11/22), followed by HNF1B (5/22). The rest of the variants were found in the NEUROD1 and HNF1A genes. We identified one novel variant in the GCK gene: c.596T>C, p.Val199Ala. The applied genetic tests excluded the suspected diagnosis of MODY in two patients and revealed variants in other genes possibly associated with the patient’s clinical phenotype.
Conclusions: In our group of MODY patients most variants were found in the GCK gene, followed by variants in HNF1B, NEUROD1, and HNF1A genes. The combined NGS and MLPA-based genetic tests presented a comprehensive approach for analysing patients with suspected MODY diabetes and provided a successful differential diagnosis of MODY subtypes.

Abstract

Introduction: Maturity onset diabetes of the young (MODY) is a rare form of monogenic diabetes. Being clinically and genetically heterogeneous, it is often misdiagnosed as type 1 or type 2 diabetes, leading to inappropriate therapy. MODY is caused by a single gene mutation. Thirteen genes, defining 13 subtypes, have been identified to cause MODY. A correct diagnosis is important for the right therapy, prognosis, and genetic counselling.
Material and methods: Twenty-nine unrelated paediatric patients clinically suspected of having MODY diabetes were analysed using TruSight One panel for next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) assay.
Results: In this study we identified variants in MODY genes in 22 out of 29 patients (75.9%). Using two genetic tests, NGS and MLPA, we detected both single nucleotide variants and large deletions in patients. Most of the patients harboured a variant in the GCK gene (11/22), followed by HNF1B (5/22). The rest of the variants were found in the NEUROD1 and HNF1A genes. We identified one novel variant in the GCK gene: c.596T>C, p.Val199Ala. The applied genetic tests excluded the suspected diagnosis of MODY in two patients and revealed variants in other genes possibly associated with the patient’s clinical phenotype.
Conclusions: In our group of MODY patients most variants were found in the GCK gene, followed by variants in HNF1B, NEUROD1, and HNF1A genes. The combined NGS and MLPA-based genetic tests presented a comprehensive approach for analysing patients with suspected MODY diabetes and provided a successful differential diagnosis of MODY subtypes.

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Keywords

MODY; NGS; MLPA; differential diagnosis

About this article
Title

The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young

Journal

Endokrynologia Polska

Issue

Vol 70, No 1 (2019)

Pages

28-36

Published online

2018-09-21

DOI

10.5603/EP.a2018.0064

Pubmed

30259503

Bibliographic record

Endokrynologia Polska 2019;70(1):28-36.

Keywords

MODY
NGS
MLPA
differential diagnosis

Authors

Jovana Komazec
Vera Zdravkovic
Silvija Sajic
Maja Jesic
Marina Andjelkovic
Sonja Pavlovic
Milena Ugrin

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