Yu Ding, Qianwen Zhang, Shiyang Gao, Juan Li, Guoying Chang, Yirou Wang, Libo Wang, Xin Li, Yao Chen, Ru-En Yao, Tingting Yu, Niu Li, Dan Lou, Xiumin Wang
{"title":"关注与儿童成熟型糖尿病相关的罕见变异。","authors":"Yu Ding, Qianwen Zhang, Shiyang Gao, Juan Li, Guoying Chang, Yirou Wang, Libo Wang, Xin Li, Yao Chen, Ru-En Yao, Tingting Yu, Niu Li, Dan Lou, Xiumin Wang","doi":"10.1155/pedi/8155443","DOIUrl":null,"url":null,"abstract":"<p><p><b>Background:</b> In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). <b>Methods:</b> From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next-generation sequencing (NGS) was performed at the Shanghai Children's Medical Center. Patients' clinical and laboratory findings were recorded preceding follow-ups. Candidate variants were verified using Sanger sequencing. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines. <b>Results:</b> Genetic testing was performed in 175 children. MODY-related pathogenic or likely pathogenic gene variants were identified in 30 patients from different families. Of these, 11 were diagnosed with <i>GCK</i>-MODY (36.7%), six with <i>INS</i>-MODY (20%), five with <i>HNF1A</i>-MODY (16.7%), five with <i>ABCC8</i>-MODY (16.7%), two with <i>HNF1B</i>-MODY (6.7%) and one with <i>HNF4A</i>-MODY (3.3%). There was one shift variant and seven splice-site variants, and the rest were missense variants. We discovered six novel variants. Of the 30 patients, 63.3% had a family history of diabetes, 13.3% had diabetic ketoacidosis (DKA), and 16.7% had positive diabetes-associated autoantibodies. The diabetes phenotype of patients with the <i>INS</i> variant was similar to that of patients with type 1 diabetes. All patients, including those having positive autoantibodies, required long-term insulin therapy during follow-ups. Four patients with the <i>ABCC8</i> variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. <b>Conclusion:</b> Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. <i>GCK</i>-MODY is the most common type of MODY, and patients with <i>INS</i> variant account for a relatively large proportion of MODY cases in our cohort.</p>","PeriodicalId":19797,"journal":{"name":"Pediatric Diabetes","volume":"2025 ","pages":"8155443"},"PeriodicalIF":3.9000,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017003/pdf/","citationCount":"0","resultStr":"{\"title\":\"Focusing on Rare Variants Related to Maturity-Onset Diabetes of the Young in Children.\",\"authors\":\"Yu Ding, Qianwen Zhang, Shiyang Gao, Juan Li, Guoying Chang, Yirou Wang, Libo Wang, Xin Li, Yao Chen, Ru-En Yao, Tingting Yu, Niu Li, Dan Lou, Xiumin Wang\",\"doi\":\"10.1155/pedi/8155443\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). <b>Methods:</b> From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next-generation sequencing (NGS) was performed at the Shanghai Children's Medical Center. Patients' clinical and laboratory findings were recorded preceding follow-ups. Candidate variants were verified using Sanger sequencing. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines. <b>Results:</b> Genetic testing was performed in 175 children. MODY-related pathogenic or likely pathogenic gene variants were identified in 30 patients from different families. Of these, 11 were diagnosed with <i>GCK</i>-MODY (36.7%), six with <i>INS</i>-MODY (20%), five with <i>HNF1A</i>-MODY (16.7%), five with <i>ABCC8</i>-MODY (16.7%), two with <i>HNF1B</i>-MODY (6.7%) and one with <i>HNF4A</i>-MODY (3.3%). There was one shift variant and seven splice-site variants, and the rest were missense variants. We discovered six novel variants. Of the 30 patients, 63.3% had a family history of diabetes, 13.3% had diabetic ketoacidosis (DKA), and 16.7% had positive diabetes-associated autoantibodies. The diabetes phenotype of patients with the <i>INS</i> variant was similar to that of patients with type 1 diabetes. All patients, including those having positive autoantibodies, required long-term insulin therapy during follow-ups. Four patients with the <i>ABCC8</i> variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. <b>Conclusion:</b> Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. <i>GCK</i>-MODY is the most common type of MODY, and patients with <i>INS</i> variant account for a relatively large proportion of MODY cases in our cohort.</p>\",\"PeriodicalId\":19797,\"journal\":{\"name\":\"Pediatric Diabetes\",\"volume\":\"2025 \",\"pages\":\"8155443\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-01-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12017003/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/pedi/8155443\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/pedi/8155443","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Focusing on Rare Variants Related to Maturity-Onset Diabetes of the Young in Children.
Background: In this study, we analysed the clinical and genetic characteristics and follow-up data of patients with maturity-onset diabetes of the young (MODY). Methods: From January 2015 to December 2022, patients with persistent hyperglycaemia suspected of having monogenic diabetes or diabetes syndrome were recruited, and next-generation sequencing (NGS) was performed at the Shanghai Children's Medical Center. Patients' clinical and laboratory findings were recorded preceding follow-ups. Candidate variants were verified using Sanger sequencing. Variant pathogenicity was evaluated according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Genetic testing was performed in 175 children. MODY-related pathogenic or likely pathogenic gene variants were identified in 30 patients from different families. Of these, 11 were diagnosed with GCK-MODY (36.7%), six with INS-MODY (20%), five with HNF1A-MODY (16.7%), five with ABCC8-MODY (16.7%), two with HNF1B-MODY (6.7%) and one with HNF4A-MODY (3.3%). There was one shift variant and seven splice-site variants, and the rest were missense variants. We discovered six novel variants. Of the 30 patients, 63.3% had a family history of diabetes, 13.3% had diabetic ketoacidosis (DKA), and 16.7% had positive diabetes-associated autoantibodies. The diabetes phenotype of patients with the INS variant was similar to that of patients with type 1 diabetes. All patients, including those having positive autoantibodies, required long-term insulin therapy during follow-ups. Four patients with the ABCC8 variant were unable to switch to oral sulfonylurea therapy and continued insulin therapy. Conclusion: Genetic testing is helpful for the precise diagnosis and treatment of patients with MODY, including those with DKA history and positive diabetes autoantibody. GCK-MODY is the most common type of MODY, and patients with INS variant account for a relatively large proportion of MODY cases in our cohort.
期刊介绍：
Pediatric Diabetes is a bi-monthly journal devoted to disseminating new knowledge relating to the epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes in childhood and adolescence. The aim of the journal is to become the leading vehicle for international dissemination of research and practice relating to diabetes in youth. Papers are considered for publication based on the rigor of scientific approach, novelty, and importance for understanding mechanisms involved in the epidemiology and etiology of this disease, especially its molecular, biochemical and physiological aspects. Work relating to the clinical presentation, course, management and outcome of diabetes, including its physical and emotional sequelae, is considered. In vitro studies using animal or human tissues, whole animal and clinical studies in humans are also considered. The journal reviews full-length papers, preliminary communications with important new information, clinical reports, and reviews of major topics. Invited editorials, commentaries, and perspectives are a regular feature. The editors, based in the USA, Europe, and Australasia, maintain regular communications to assure rapid turnaround time of submitted manuscripts.
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