Abstract
Aims: Maturity-onset diabetes of the young (MODY) is an early-onset, monogenic diabetes with an autosomal dominant inheritance pattern. Single gene mutations that cause dysfunction in pancreatic beta cells are responsible for MODY etiology. In this study, we investigated the genetic variants involved in the etiopathogenesis of MODY in our region.
Methods: Between May 2018 and April 2023, 40 pediatric patients (n=25 females, n=15 males) with a clinical diagnosis of MODY were evaluated by targeted genome sequencing.
Results: Among the 40 pediatric patients included in this study, variants in MODY-associated genes were detected in 21 patients (52.5%), eight (38.09%), of which were pathogenic (38.09%), five (23.8%) were probable pathogenic, and eight (38.09%), were of uncertain significance.
Conclusion: In this study, genetic diagnostic yield (including pathogenic and likely pathogenic variants) was detected in 32.5% (13/40) patients with MODY using targeted genome sequencing analysis. This rate is consistent with other studies. However, unlike other similar studies, the MODY12 subtype was the second most frequent in our study. In addition, nine novel variants were reported, including ABCC8 (n=3), CEL (n=2), KLF11 (n=1), GCK (n=1), HNF1A (n=1), and HNF1B (n=1) genes. We have presented clinical findings to improve genotype-phenotype correlation in the literature for novel variants.
References
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- Karahan İ, Çifci A. Oruç tutan diyabet hastalarının oruç esnasında gelişen istenmeyen olaylarına geriye dönük bakış. Anatolian Curr Med J. 2019;1(2):20-22.
- Durak MB, Yeşilaltay A. The effect of long-term use of pioglitazone on bone mineral density in patients with diabetes mellitus. Anatolian Curr Med J. 2023;5(3):261-265.
- Demirci H, Yurtcu E, Ergun MA, Yazici AC, Karasu C, Yetkin I. Calpain 10 SNP-44 gene polymorphism affects susceptibility to type 2 diabetes mellitus and diabetic-related conditions. Genetic Testing. 2008;12(2):305-309.
- Yalçıntepe S, Özgüç Çömlek F, Gürkan H, et al. The application of next generation sequencing maturity onset diabetes of the young gene panel in Turkish patients from Trakya region. J Clin Res Pediatr Endocrinol. 2021;13(3):320-331.
- Firdous P, Nissar K, Ali S, et al. Genetic testing of maturity-onset diabetes of the young current status and future perspectives. Front Endocrinol. 2018;9:253.
- Araslı Yılmaz A, Elmaoğulları S, Tayfun M, et al. Mody type 2 case due to newly diagnosed mutations in the glucokinase. Turkiye Klinikleri J Case Rep. 2016;24(2 Suppl 1):1-5.
- Ellard S, Bellanné-Chantelot C, Hattersley AT, European Molecular Genetics Quality Network (EMQN) MODY group. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008;51(4):546-553.
- Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for molecular pathology. Gen Med. 2015;17(5):405-423.
- Chen Y, Zhao J, Li X, et al. Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China. Chinese Med J. 2023;136(1):56-64.
- Kanca Demirci D, Gül N, Satman I, et al. Gençlerin erişkin başlangıçlı diyabeti (MODY) sorumlu HNF4A, GCK ve HNF1 gen varyasyonlarının dünya genelinde coğrafik dağılımı. Haliç Üniversitesi Fen Bilimleri Derg. 2021;4(1):41-68.
- Yılmaz-Ağladıoğlu S, Aycan Z, Çetinkaya S, et al. Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing. J Pediatr Endocrinol Metab. 2016;29(4):487-496.
- Demiral M, Çelebi HBG, Cander S, Yerci O, Eren E, Demirbilek H. Two opposite phenotypes of glucose disorders in a family with heterozygous P.SER453LEU (C.1358C> T) mutation in the glucokinase (GCK) gene: maturity onset diabetes in young and insulinoma. Acta Endocrinol (Buchar). 2022;18(4):458-465.
- Wang Y, Kang C, Tong Q, et al. A case report of maturity-onset diabetes of the young (MODY12) in a Chinese Han patient with a novel ABCC8 gene mutation. Medicine (Baltimore). 2022;101(49):e32139.
- Li J, Wang X, Mao H, et al. Precision therapy for three Chinese families with maturity-onset diabetes of the young (MODY12). Front Endocrinol (Lausanne). 2022;13:858096.
- Gökşen D, Yeşilkaya E, Özen S, et al. Molecular diagnosis of monogenic diabetes and their clinical/laboratory features in Turkish children. J Clin Res Pediatr Endocrinol. 2021;13(4):433-438.
- Doğan M, Eröz R, Bolu S, et al. Study of ten causal genes in Turkish patients with clinically suspected maturity-onset diabetes of the young (MODY) using a targeted next-generation sequencing panel. Molecul Biol Rep. 2022;49(8):7483-7495.
- Patel KA, Ozbek MN, Yildiz M, et al. Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics. Diabetologia. 2022;65(2):336-342.
- Peixoto-Barbosa R, Reis AF, Giuffrida F. Update on clinical screening of maturity-onset diabetes of the young (MODY). Diabetol Metab Syndrome. 2020;12(1):1-14.
- Tatsi EB, Kanaka‐Gantenbein C, Scorilas A, et al. Next generation sequencing targeted gene panel in Greek MODY patients increases diagnostic accuracy. Pediatr Diabet. 2020;21(1):28-39.
Abstract
References
- Varol H, Çifci A. Tip 2 diyabette yeni tedavi yaklaşımları: olgu örnekleriyle bakış. J Med Palliat Care. 2020;1(1):12-15.
- Karahan İ, Çifci A. Oruç tutan diyabet hastalarının oruç esnasında gelişen istenmeyen olaylarına geriye dönük bakış. Anatolian Curr Med J. 2019;1(2):20-22.
- Durak MB, Yeşilaltay A. The effect of long-term use of pioglitazone on bone mineral density in patients with diabetes mellitus. Anatolian Curr Med J. 2023;5(3):261-265.
- Demirci H, Yurtcu E, Ergun MA, Yazici AC, Karasu C, Yetkin I. Calpain 10 SNP-44 gene polymorphism affects susceptibility to type 2 diabetes mellitus and diabetic-related conditions. Genetic Testing. 2008;12(2):305-309.
- Yalçıntepe S, Özgüç Çömlek F, Gürkan H, et al. The application of next generation sequencing maturity onset diabetes of the young gene panel in Turkish patients from Trakya region. J Clin Res Pediatr Endocrinol. 2021;13(3):320-331.
- Firdous P, Nissar K, Ali S, et al. Genetic testing of maturity-onset diabetes of the young current status and future perspectives. Front Endocrinol. 2018;9:253.
- Araslı Yılmaz A, Elmaoğulları S, Tayfun M, et al. Mody type 2 case due to newly diagnosed mutations in the glucokinase. Turkiye Klinikleri J Case Rep. 2016;24(2 Suppl 1):1-5.
- Ellard S, Bellanné-Chantelot C, Hattersley AT, European Molecular Genetics Quality Network (EMQN) MODY group. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia. 2008;51(4):546-553.
- Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for molecular pathology. Gen Med. 2015;17(5):405-423.
- Chen Y, Zhao J, Li X, et al. Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China. Chinese Med J. 2023;136(1):56-64.
- Kanca Demirci D, Gül N, Satman I, et al. Gençlerin erişkin başlangıçlı diyabeti (MODY) sorumlu HNF4A, GCK ve HNF1 gen varyasyonlarının dünya genelinde coğrafik dağılımı. Haliç Üniversitesi Fen Bilimleri Derg. 2021;4(1):41-68.
- Yılmaz-Ağladıoğlu S, Aycan Z, Çetinkaya S, et al. Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing. J Pediatr Endocrinol Metab. 2016;29(4):487-496.
- Demiral M, Çelebi HBG, Cander S, Yerci O, Eren E, Demirbilek H. Two opposite phenotypes of glucose disorders in a family with heterozygous P.SER453LEU (C.1358C> T) mutation in the glucokinase (GCK) gene: maturity onset diabetes in young and insulinoma. Acta Endocrinol (Buchar). 2022;18(4):458-465.
- Wang Y, Kang C, Tong Q, et al. A case report of maturity-onset diabetes of the young (MODY12) in a Chinese Han patient with a novel ABCC8 gene mutation. Medicine (Baltimore). 2022;101(49):e32139.
- Li J, Wang X, Mao H, et al. Precision therapy for three Chinese families with maturity-onset diabetes of the young (MODY12). Front Endocrinol (Lausanne). 2022;13:858096.
- Gökşen D, Yeşilkaya E, Özen S, et al. Molecular diagnosis of monogenic diabetes and their clinical/laboratory features in Turkish children. J Clin Res Pediatr Endocrinol. 2021;13(4):433-438.
- Doğan M, Eröz R, Bolu S, et al. Study of ten causal genes in Turkish patients with clinically suspected maturity-onset diabetes of the young (MODY) using a targeted next-generation sequencing panel. Molecul Biol Rep. 2022;49(8):7483-7495.
- Patel KA, Ozbek MN, Yildiz M, et al. Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics. Diabetologia. 2022;65(2):336-342.
- Peixoto-Barbosa R, Reis AF, Giuffrida F. Update on clinical screening of maturity-onset diabetes of the young (MODY). Diabetol Metab Syndrome. 2020;12(1):1-14.
- Tatsi EB, Kanaka‐Gantenbein C, Scorilas A, et al. Next generation sequencing targeted gene panel in Greek MODY patients increases diagnostic accuracy. Pediatr Diabet. 2020;21(1):28-39.
Details
| Primary Language | English |
|---|---|
| Subjects | Medical Genetics (Excl. Cancer Genetics) |
| Journal Section | Research Articles |
| Authors | |
| Early Pub Date | October 26, 2023 |
| Publication Date | October 27, 2023 |
| Published in Issue | Year 2023 Volume: 5 Issue: 4 |
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