The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young
Аутори
Komazec, JovanaZdravković, Vera
Sajić, Silvija
Jesić, Maja
Anđelković, Marina
Pavlović, Sonja
Ugrin, Milena
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 r...est of the variants were found in the NEUROD1 and HNF1A genes. We identified one novel variant in the GCK gene: c.596T gt 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.
Кључне речи:
NGS / MODY / MLPA / differential diagnosisИзвор:
Endokrynologia Polska, 2019, 70, 1, 28-36Издавач:
- Via Medica, Gdansk
Финансирање / пројекти:
- Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.5603/EP.a2018.0064
ISSN: 0423-104X
PubMed: 30259503
WoS: 000463867600004
Scopus: 2-s2.0-85062090387
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Komazec, Jovana AU - Zdravković, Vera AU - Sajić, Silvija AU - Jesić, Maja AU - Anđelković, Marina AU - Pavlović, Sonja AU - Ugrin, Milena PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1245 AB - 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 gt 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. PB - Via Medica, Gdansk T2 - Endokrynologia Polska T1 - The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young EP - 36 IS - 1 SP - 28 VL - 70 DO - 10.5603/EP.a2018.0064 ER -
@article{ author = "Komazec, Jovana and Zdravković, Vera and Sajić, Silvija and Jesić, Maja and Anđelković, Marina and Pavlović, Sonja and Ugrin, Milena", year = "2019", 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 gt 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.", publisher = "Via Medica, Gdansk", journal = "Endokrynologia Polska", title = "The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young", pages = "36-28", number = "1", volume = "70", doi = "10.5603/EP.a2018.0064" }
Komazec, J., Zdravković, V., Sajić, S., Jesić, M., Anđelković, M., Pavlović, S.,& Ugrin, M.. (2019). The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young. in Endokrynologia Polska Via Medica, Gdansk., 70(1), 28-36. https://doi.org/10.5603/EP.a2018.0064
Komazec J, Zdravković V, Sajić S, Jesić M, Anđelković M, Pavlović S, Ugrin M. The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young. in Endokrynologia Polska. 2019;70(1):28-36. doi:10.5603/EP.a2018.0064 .
Komazec, Jovana, Zdravković, Vera, Sajić, Silvija, Jesić, Maja, Anđelković, Marina, Pavlović, Sonja, Ugrin, Milena, "The importance of combined NGS and MLPA genetic tests for differential diagnosis of maturity onset diabetes of the young" in Endokrynologia Polska, 70, no. 1 (2019):28-36, https://doi.org/10.5603/EP.a2018.0064 . .