avkАрхивъ внутренней медициныThe Russian Archives of Internal Medicine2226-67042411-6564“SINAPS” LLC10.20514/2226-6704-2022-12-6-430-437avk-1532Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESДИАГНОСТИКА И ЛЕЧЕНИЕ МОНОГЕННЫХ ФОРМ САХАРНОГО ДИАБЕТА: В ФОКУСЕ MODY-ДИАБЕТDiagnosis and Treatment of Monogenic Forms of Diabetes Mellitus: Focus on Mody-Diabeteshttps://orcid.org/0000-0003-4973-039XАйтбаевК. А.AitbaevK. A.

Бишкек

Bishkek

https://orcid.org/0000-0001-8513-9279МуркамиловИ. Т.MurkamilovI. T.

Илхом Торобекович Муркамилов

Бишкек

Ilkhom T. Murkamilov

Bishkek

murkamilov.i@mail.ruhttps://orcid.org/0000-0002-7653-0433МуркамиловаЖ. А.MurkamilovaZh. A.

Бишкек

Bishkek

https://orcid.org/0000-0002-2682-4417ФоминВ. В.FominV. V.

Москва

Moscow

https://orcid.org/0000-0003-3007-8127КудайбергеноваИ. О.KudaibergenovaI. O

Бишкек

Bishkek

https://orcid.org/0000-0003-0632-6653ЮсуповФ. А.YusupovF. A.

Ош

Osh

Научно-исследовательский институт молекулярной биологии и медициныКыргызстанScientific and research Institute of molecular biology and medicineKyrgyzstanКыргызская государственная медицинская академия имени И.К. Ахунбаева; ГОУ ВПО Кыргызско-Российский славянский университетКыргызстанI.K. Akhunbaev Kyrgyz State Medical Academy; SEI HPE Kyrgyz Russian Slavic UniversityKyrgyzstanГОУ ВПО Кыргызско-Российский славянский университетРоссияSEI HPE Kyrgyz Russian Slavic UniversityRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияFSAEI HE First Moscow State Medical University named after I.M. SechenovRussian FederationКыргызская государственная медицинская академия имени И.К. АхунбаеваКыргызстанI.K. Akhunbaev Kyrgyz State Medical AcademyKyrgyzstanОшский государственный университетКыргызстанOsh State UniversityKyrgyzstan202229112022126430437Copyright © Айтбаев К.А., Муркамилов И.Т., Муркамилова Ж.А., Фомин В.В., Кудайбергенова И.О., Юсупов Ф.А., 20222022Айтбаев К.А., Муркамилов И.Т., Муркамилова Ж.А., Фомин В.В., Кудайбергенова И.О., Юсупов Ф.А.Aitbaev K.A., Murkamilov I.T., Murkamilova Z.A., Fomin V.V., Kudaibergenova I.o., Yusupov F.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medarhive.ru/jour/article/view/1532

Диабет зрелого возраста у молодых (MODY) является наиболее распространенной формой моногенного диабета, возникающего в результате мутации одного гена. Он характеризуется легкой гипергликемией, аутосомно-доминантным типом наследования, ранним началом диабета (<25 лет), сохранением эндогенной секреции инсулина, а также наличием подтипов, различающихся клинически и генетически. В настоящее время идентифицировано 14 подтипов MODY, отличающихся частотой возникновения, клиническими особенностями, тяжестью диабета и связанными с ним осложнениями, а также ответом на лечение. Этот тип диабета, зачастую некорректно диагностируется как сахарный диабет типа 1 или типа 2. Причина тому — клиническое сходство с другими типами диабета, высокая стоимость и ограниченный доступ к генетическому тестированию, а также недостаточная осведомлённость клиницистов. В результате несвоевременной диагностики пациенты не получают надлежащего эффективного лечения, отличного от терапии диабета 1 и 2 типов. Цель данного обзора — повысить осведомлённость клиницистов о MODY-диабете, акцентировав внимание на обновленной информации о методах диагностики и лечения 14 подтипов.

Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes resulting from a single gene mutation. It is characterized by mild hyperglycemia, autosomal dominant inheritance, early onset diabetes (<25 years), persistence of endogenous insulin secretion, and clinically and genetically distinct subtypes. Currently, 14 subtypes of MODY have been identified, differing in incidence, clinical features, severity of diabetes and associated complications, and response to treatment. This type of diabetes is mostly misdiagnosed as type 1 or type 2 diabetes mellitus due to clinical similarities to other types of diabetes, high cost and limited access to genetic testing, and lack of clinician awareness. As a result, thousands of patients do not receive proper treatment. Accurate diagnosis would allow for more effective therapeutic treatments other than those used for type 1 and type 2 diabetes. The purpose of this review is to raise clinicians’ awareness of MODY diabetes by focusing on updated information on methods for diagnosing and treating its 14 subtypes.

сахарный диабет зрелого возраста у молодыхсахарный диабетгенетическое тестированиегенные мутацииHNF1Aглюкокиназа (GCK)Maturity-Onset Diabetes of the Young (MODY)diabetesgenetic testinggene mutationsHNF1Aglucokinase (GCK)ReferencesPihoker C, Gilliam LK, Ellard S et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: Results from the SEARCH for Diabetes in Youth. J. Clin. Endocrinol. Metab. 2013; 98: 4055–4062. https://doi.org/10.1210/jc.2013-1279Pihoker C, Gilliam LK, Ellard S et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: Results from the SEARCH for Diabetes in Youth. J. Clin. Endocrinol. Metab. 2013; 98: 4055–4062. https://doi.org/10.1210/jc.2013-1279Дедов И.И., Шестакова М.В., Майоров А.Ю. и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. М. 2021; 24(S1). 222 с.Dedov II, Shestakova MV, Mayorov AYu et al. Standards of specialized diabetes care. M. 2021; 24(S1). 222 p. [In Russian].Mohan V, Sharp PS, Aber VR et al. Insulin resistance in maturity onset diabetes of the young. Diabete Metab. 1987;13(3):193-197.Mohan V, Sharp PS, Aber VR et al. Insulin resistance in maturity onset diabetes of the young. Diabete Metab. 1987;13(3):193-197.Kim SH. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know? Diabetes Metab. J. 2015; 39: 468–477.https://doi.org/10.4093/dmj.2015.39.6.468Kim SH. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know? Diabetes Metab. J. 2015; 39: 468–477.https://doi.org/10.4093/dmj.2015.39.6.468Shields BM, Hicks S, Shepherd M et al. Maturity-onset diabetes of the young (MODY): How many cases are we missing? Diabetologia. 2010; 53: 2504–2508. https://doi.org/10.1007/s00125-010-1799-4Shields BM, Hicks S, Shepherd M et al. Maturity-onset diabetes of the young (MODY): How many cases are we missing? Diabetologia. 2010; 53: 2504–2508. https://doi.org/10.1007/s00125-010-1799-4Heuvel-Borsboom H, de Valk HW, Losekoot M, et al. Maturity onset diabetes of the young: Seek and you will find. Neth. J. Med. 2016; 74: 193–200.Heuvel-Borsboom H, de Valk HW, Losekoot M, et al. Maturity onset diabetes of the young: Seek and you will find. Neth. J. Med. 2016; 74: 193–200.Malik RA, Shaikh S. Monogenic diabetes: Importance of genetic testing. Middle East J. Fam. Med. 2020; 18: 78–86.Malik RA, Shaikh S. Monogenic diabetes: Importance of genetic testing. Middle East J. Fam. Med. 2020; 18: 78–86.Peixoto-Barbosa R, Reis AF, Giuffrida FMA. Update on clinical screening of maturity-onset diabetes of the young (MODY). Diabetol. Metab. Syndr. 2020; 12:50. https://doi.org/10.1186/s13098-020-00557-9Peixoto-Barbosa R, Reis AF, Giuffrida FMA. Update on clinical screening of maturity-onset diabetes of the young (MODY). Diabetol. Metab. Syndr. 2020; 12:50. https://doi.org/10.1186/s13098-020-00557-9Stanik J, Dusatkova P, Cinek O et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 2014; 57: 480–484. https://doi.org/10.1007/s00125-013-3119-2Stanik J, Dusatkova P, Cinek O et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 2014; 57: 480–484. https://doi.org/10.1007/s00125-013-3119-2Ellard S, Bellanné-Chantelot C, Hattersley AT. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51: 546–553. https://doi.org/10.1007/s00125-008-0942-yEllard S, Bellanné-Chantelot C, Hattersley AT. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008; 51: 546–553. https://doi.org/10.1007/s00125-008-0942-yThanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ 2011; 343: d6044. https://doi.org/10.1136/bmj.d6044Thanabalasingham G, Owen KR. Diagnosis and management of maturity onset diabetes of the young (MODY). BMJ 2011; 343: d6044. https://doi.org/10.1136/bmj.d6044Pearson ER, Starkey BJ, Powell RJ et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003; 362: 1275–1281. https://doi.org/10.1016/S0140-6736(03)14571-0Pearson ER, Starkey BJ, Powell RJ et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003; 362: 1275–1281. https://doi.org/10.1016/S0140-6736(03)14571-0Timsit J, Saint-Martin C, Dubois-Laforgue D, et al. Searching for Maturity-Onset Diabetes of the Young (MODY): When and What for? Can. J. Diabetes 2016; 40: 455–461. https://doi.org/ 10.1016/j. jcjd.2015.12.005Timsit J, Saint-Martin C, Dubois-Laforgue D, et al. Searching for Maturity-Onset Diabetes of the Young (MODY): When and What for? Can. J. Diabetes 2016; 40: 455–461. https://doi.org/ 10.1016/j. jcjd.2015.12.005Amed S, Oram R. Maturity-Onset Diabetes of the Young (MODY): Making the Right Diagnosis to Optimize Treatment. Can. J. Diabetes 2016; 40: 449–454. https://doi.org/10.1016/j.jcjd.2016.03.002Amed S, Oram R. Maturity-Onset Diabetes of the Young (MODY): Making the Right Diagnosis to Optimize Treatment. Can. J. Diabetes 2016; 40: 449–454. https://doi.org/10.1016/j.jcjd.2016.03.002Delvecchio M, Pastore C, Giordano P. Treatment Options for MODY Patients: A Systematic Review of Literature. Diabetes Ther. 2020; 11: 1667–1685. doi: 10.1007/s13300-020-00864-4Delvecchio M, Pastore C, Giordano P. Treatment Options for MODY Patients: A Systematic Review of Literature. Diabetes Ther. 2020; 11: 1667–1685. doi: 10.1007/s13300-020-00864-4Yamagata K, Oda N, Kaisaki PJ et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 1996; 384: 455–458. https://doi.org/10.1038/384455a0Yamagata K, Oda N, Kaisaki PJ et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature 1996; 384: 455–458. https://doi.org/10.1038/384455a0Nkonge KM, Nkonge DK, Nkonge TN. The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY). Clin. Diabetes Endocrinol. 2020; 6: 20. https://doi.org/10.1186/s40842-020-00112-5Nkonge KM, Nkonge DK, Nkonge TN. The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY). Clin. Diabetes Endocrinol. 2020; 6: 20. https://doi.org/10.1186/s40842-020-00112-5Stride A, Vaxillaire M, Tuomi T et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia 2002; 45: 427–435. https://doi.org/10.1007/s00125-001-0770-9Stride A, Vaxillaire M, Tuomi T et al. The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia 2002; 45: 427–435. https://doi.org/10.1007/s00125-001-0770-9Urakami T. Maturity-onset diabetes of the young (MODY): Current perspectives on diagnosis and treatment. Diabetes Metab. Syndr. Obes. 2019; 12: 1047–1056. https://doi.org/10.2147/DMSO.S179793Urakami T. Maturity-onset diabetes of the young (MODY): Current perspectives on diagnosis and treatment. Diabetes Metab. Syndr. Obes. 2019; 12: 1047–1056. https://doi.org/10.2147/DMSO.S179793Kanwal A, Fazal S, Ismail M, et al. A narrative insight to maturityonset diabetes of the young. Clin. Rev. Opin. 2011; 3: 6–13.Kanwal A, Fazal S, Ismail M, et al. A narrative insight to maturityonset diabetes of the young. Clin. Rev. Opin. 2011; 3: 6–13.Matschinsky F, Liang Y, Kesavan P et al. Glucokinase as pancreatic beta cell glucose sensor and diabetes gene. J. Clin. Investig. 1993; 92: 2092–2098. https://doi.org/10.1172/JCI116809Matschinsky F, Liang Y, Kesavan P et al. Glucokinase as pancreatic beta cell glucose sensor and diabetes gene. J. Clin. Investig. 1993; 92: 2092–2098. https://doi.org/10.1172/JCI116809Hulín J, Škopková M, Valkovičová T et al. Clinical implications of the glucokinase impaired function—GCK MODY today. Physiol. Res. 2020; 69: 995–1011. https://doi.org/10.33549/physiolres.934487Hulín J, Škopková M, Valkovičová T et al. Clinical implications of the glucokinase impaired function—GCK MODY today. Physiol. Res. 2020; 69: 995–1011. https://doi.org/10.33549/physiolres.934487Rudland VL. Diagnosis and management of glucokinase monogenic diabetes in pregnancy: Current perspectives. Diabetes Metab. Syndr. Obes. 2019; 12: 1081–1089. https://doi.org/10.2147/DMSO.S186610Rudland VL. Diagnosis and management of glucokinase monogenic diabetes in pregnancy: Current perspectives. Diabetes Metab. Syndr. Obes. 2019; 12: 1081–1089. https://doi.org/10.2147/DMSO.S186610Valkovicova T, Skopkova M, Stanik J, et al. Novel insights into genetics and clinics of the HNF1A-MODY. Endocr. Regul. 2019; 53: 110–134. https://doi.org/10.2478/enr-2019-0013Valkovicova T, Skopkova M, Stanik J, et al. Novel insights into genetics and clinics of the HNF1A-MODY. Endocr. Regul. 2019; 53: 110–134. https://doi.org/10.2478/enr-2019-0013Docena MK, Faiman C, Stanley CM, Pantalone KM. Mody-3: Novel HNF1A mutation and the utility of glucagon-like peptide (GLP)-1 receptor agonist therapy. Endocr. Pract. 2014; 20: 107–111. https://doi.org/10.4158/EP13254.ORDocena MK, Faiman C, Stanley CM, Pantalone KM. Mody-3: Novel HNF1A mutation and the utility of glucagon-like peptide (GLP)-1 receptor agonist therapy. Endocr. Pract. 2014; 20: 107–111. https://doi.org/10.4158/EP13254.ORKim SK, Selleri L, Lee JS et al. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Nat. Genet. 2002; 30: 430–435. https://doi.org/10.1038/ng860Kim SK, Selleri L, Lee JS et al. Pbx1 inactivation disrupts pancreas development and in Ipf1-deficient mice promotes diabetes mellitus. Nat. Genet. 2002; 30: 430–435. https://doi.org/10.1038/ng860Schwitzgebel V, Mamin A, Brun T et al. Agenesis of Human Pancreas due to Decreased Half-Life of Insulin Promoter Factor 1. J. Clin. Endocrinol. Metab. 2003; 88: 4398–4406. https://doi.org/10.1210/jc.2003-030046Schwitzgebel V, Mamin A, Brun T et al. Agenesis of Human Pancreas due to Decreased Half-Life of Insulin Promoter Factor 1. J. Clin. Endocrinol. Metab. 2003; 88: 4398–4406. https://doi.org/10.1210/jc.2003-030046Stoffers DA, Zinkin NT, Stanojevic V et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat. Genet. 1997; 15: 106–110. https://doi.org/10.1038/ng0197-106Stoffers DA, Zinkin NT, Stanojevic V et al. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat. Genet. 1997; 15: 106–110. https://doi.org/10.1038/ng0197-106Deng M, Xiao X, Zhou L, et al. First Case Report of Maturity- Onset Diabetes of the Young Type 4 Pedigree in a Chinese Family. Front. Endocrinol. 2019; 10: 406. https://doi.org/10.3389/fendo.2019.00406Deng M, Xiao X, Zhou L, et al. First Case Report of Maturity- Onset Diabetes of the Young Type 4 Pedigree in a Chinese Family. Front. Endocrinol. 2019; 10: 406. https://doi.org/10.3389/fendo.2019.00406Mangrum C, Rush E, Shivaswamy V. Genetically Targeted Dipeptidyl Peptidase-4 Inhibitor Use in a Patient with a Novel Mutation of MODY type 4. Clin. Med. Insights Endocrinol. Diabetes. 2015; 8: 83–86. https://doi.org/10.4137/CMED.S31926Mangrum C, Rush E, Shivaswamy V. Genetically Targeted Dipeptidyl Peptidase-4 Inhibitor Use in a Patient with a Novel Mutation of MODY type 4. Clin. Med. Insights Endocrinol. Diabetes. 2015; 8: 83–86. https://doi.org/10.4137/CMED.S31926Lindner TH, Cockburn BN, Bell GI. Molecular genetics of MODY in Germany. Diabetologia.1999; 42: 121–123. https://doi.org/10.1007/s001250051128Lindner TH, Cockburn BN, Bell GI. Molecular genetics of MODY in Germany. Diabetologia.1999; 42: 121–123. https://doi.org/10.1007/s001250051128Bellanné-Chantelot C, Chauveau D, Gautier J-F et al. Clinical Spectrum Associated with Hepatocyte Nuclear Factor-1 Mutations Background: Maturity-onset diabetes of the young type 5. Ann. Intern. Med. 2004; 140: 510–517. https://doi.org/10.7326/0003-4819-140-7-200404060-00009Bellanné-Chantelot C, Chauveau D, Gautier J-F et al. Clinical Spectrum Associated with Hepatocyte Nuclear Factor-1 Mutations Background: Maturity-onset diabetes of the young type 5. Ann. Intern. Med. 2004; 140: 510–517. https://doi.org/10.7326/0003-4819-140-7-200404060-00009Hattersley AT, Greeley SAW, Polak M et al. ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr. Diabetes. 2018; 19: 47–63. https://doi.org/10.1111/pedi.12772Hattersley AT, Greeley SAW, Polak M et al. ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr. Diabetes. 2018; 19: 47–63. https://doi.org/10.1111/pedi.12772Firdous 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. https://doi.org/10.3389/fendo.2018.00253Firdous 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. https://doi.org/10.3389/fendo.2018.00253Malecki MT, Jhala US, Antonellis A et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat. Genet. 1999; 23: 323–328. https://doi.org/10.1038/15500Malecki MT, Jhala US, Antonellis A et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nat. Genet. 1999; 23: 323–328. https://doi.org/10.1038/15500Horikawa Y, Enya M. Genetic Dissection and Clinical Features of MODY6 (NEUROD1-MODY). Curr. Diab. Rep. 2019; 19(3):12. https://doi.org/10.1007/s11892-019-1130-9Horikawa Y, Enya M. Genetic Dissection and Clinical Features of MODY6 (NEUROD1-MODY). Curr. Diab. Rep. 2019; 19(3):12. https://doi.org/10.1007/s11892-019-1130-9Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc. Natl. Acad. Sci. USA 2005; 102: 4807–4812. https://doi.org/10.1073/pnas.0409177102Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc. Natl. Acad. Sci. USA 2005; 102: 4807–4812. https://doi.org/10.1073/pnas.0409177102Raeder H, Johansson S, Holm PI et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat.Genet. 2006; 38: 54–62. https://doi.org/10.1038/ng1708Raeder H, Johansson S, Holm PI et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nat.Genet. 2006; 38: 54–62. https://doi.org/10.1038/ng1708Hui DY, Howles PN. Carboxyl ester lipase: Structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis. J. Lipid Res. 2002; 43: 2017–2030. https://doi.org/10.1194/jlr.r200013-jlr200Hui DY, Howles PN. Carboxyl ester lipase: Structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis. J. Lipid Res. 2002; 43: 2017–2030. https://doi.org/10.1194/jlr.r200013-jlr200Habener JF, Kemp DM, Thomas MK. Minireview: Transcriptional regulation in pancreatic development. Endocrinology. 2005; 146: 1025–1034. https://doi.org/10.1210/en.2004-1576Habener JF, Kemp DM, Thomas MK. Minireview: Transcriptional regulation in pancreatic development. Endocrinology. 2005; 146: 1025–1034. https://doi.org/10.1210/en.2004-1576Mauvais-Jarvis F, Smith SB, Le May C et al. PAX4 gene variations predispose to ketosis-prone diabetes. Hum. Mol. Genet. 2004; 13: 3151–3159. https://doi.org/10.1093/hmg/ddh341Mauvais-Jarvis F, Smith SB, Le May C et al. PAX4 gene variations predispose to ketosis-prone diabetes. Hum. Mol. Genet. 2004; 13: 3151–3159. https://doi.org/10.1093/hmg/ddh341Plengvidhya N, Kooptiwut S, Songtawee N et al. PAX4 mutations in Thais with maturity onset diabetes of the young. J. Clin. Endocrinol. Metab. 2007; 92: 2821–2826. https://doi.org/10.1093/hmg/ddh341Plengvidhya N, Kooptiwut S, Songtawee N et al. PAX4 mutations in Thais with maturity onset diabetes of the young. J. Clin. Endocrinol. Metab. 2007; 92: 2821–2826. https://doi.org/10.1093/hmg/ddh341Sujjitjoon J, Kooptiwut S, Chongjaroen N et al. Aberrant mRNA splicing of paired box 4 (PAX4) IVS7-1G>A mutation causing maturity-onset diabetes of the young, type 9. Acta Diabetol. 2016; 53: 205–216. https://doi.org/10.1007/s00592-015-0760-xSujjitjoon J, Kooptiwut S, Chongjaroen N et al. Aberrant mRNA splicing of paired box 4 (PAX4) IVS7-1G>A mutation causing maturity-onset diabetes of the young, type 9. Acta Diabetol. 2016; 53: 205–216. https://doi.org/10.1007/s00592-015-0760-xEdghill EL, Flanagan SE, Patch A-M et al. Insulin mutation screening in 1,044 patients with diabetes: Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008; 57: 1034–1042. https://doi.org/10.2337/db07-1405Edghill EL, Flanagan SE, Patch A-M et al. Insulin mutation screening in 1,044 patients with diabetes: Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. Diabetes. 2008; 57: 1034–1042. https://doi.org/10.2337/db07-1405Jang KM. Maturity-onset diabetes of the young: Update and perspectives on diagnosis and treatment. Yeungnam Univ. J. Med. 2020; 37: 13–21. https://doi.org/10.12701/yujm.2019.00409Jang KM. Maturity-onset diabetes of the young: Update and perspectives on diagnosis and treatment. Yeungnam Univ. J. Med. 2020; 37: 13–21. https://doi.org/10.12701/yujm.2019.00409Islam KB, Rabbani H, Larsson C et al. Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk. J. Immunol. 1995; 154: 1265–1272.Islam KB, Rabbani H, Larsson C et al. Molecular cloning, characterization, and chromosomal localization of a human lymphoid tyrosine kinase related to murine Blk. J. Immunol. 1995; 154: 1265–1272.Borowiec M, Liew CW, Thompson R et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc. Natl. Acad. Sci. USA. 2009; 106: 14460–14465. https://doi.org/10.1073/pnas.0906474106Borowiec M, Liew CW, Thompson R et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc. Natl. Acad. Sci. USA. 2009; 106: 14460–14465. https://doi.org/10.1073/pnas.0906474106Bonnefond A, Yengo L, Philippe J et al. Reassessment of the putative role of BLK-p.A71T loss-of-function mutation in MODY and type 2 diabetes. Diabetologia. 2013; 56: 492–496. https://doi.org/10.1007/s00125-012-2794-8Bonnefond A, Yengo L, Philippe J et al. Reassessment of the putative role of BLK-p.A71T loss-of-function mutation in MODY and type 2 diabetes. Diabetologia. 2013; 56: 492–496. https://doi.org/10.1007/s00125-012-2794-8Doddabelavangala Mruthyunjaya M, Chapla A, Hesarghatta Shyamasunder A et al. Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India. PLoS ONE. 2017; 12: e0168656. https://doi.org/10.1371/journal.pone.0168656Doddabelavangala Mruthyunjaya M, Chapla A, Hesarghatta Shyamasunder A et al. Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India. PLoS ONE. 2017; 12: e0168656. https://doi.org/10.1371/journal.pone.0168656Kapoor RR, Flanagan SE, James C et al. Hyperinsulinaemic hypoglycaemia. Arch. Dis. Child. 2009; 94: 450–457. https://doi.org/10.1136/adc.2008.148171Kapoor RR, Flanagan SE, James C et al. Hyperinsulinaemic hypoglycaemia. Arch. Dis. Child. 2009; 94: 450–457. https://doi.org/10.1136/adc.2008.148171Rafiq M, Flanagan SE, Patch A-M et al. Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care. 2008; 31: 204–209. https://doi.org/10.2337/dc07-1785Rafiq M, Flanagan SE, Patch A-M et al. Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care. 2008; 31: 204–209. https://doi.org/10.2337/dc07-1785Schenck A, Goto-Silva L, Collinet C et al. The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell. 2008; 133: 486–497. https://doi.org/10.1016/j.cell.2008.02.044Schenck A, Goto-Silva L, Collinet C et al. The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development. Cell. 2008; 133: 486–497. https://doi.org/10.1016/j.cell.2008.02.044Anik A, Catli G, Abaci A, et al. Maturity-onset diabetes of the young (MODY): An update. J. Pediatr. Endocrinol. Metab. 2015; 28:251-263.Anik A, Catli G, Abaci A, et al. Maturity-onset diabetes of the young (MODY): An update. J. Pediatr. Endocrinol. Metab. 2015; 28:251-263.

The authors declare that there are no conflicts of interest present.