Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry
| العنوان: | Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry |
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| المؤلفون: | Xiao Fan, Wendy K. Chung, Emily Breidbart, Rudolph L. Leibel, Jiancheng Guo, Patricia Lanzano, Charles A. LeDuc, Liyong Deng |
| المصدر: | J Pediatr Endocrinol Metab |
| بيانات النشر: | Walter de Gruyter GmbH, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Proband, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, New York, 030209 endocrinology & metabolism, Article, Maturity onset diabetes of the young, Germinal Center Kinases, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Molecular genetics, Exome Sequencing, Humans, Medicine, Genetic Testing, Hepatocyte Nuclear Factor 1-alpha, Registries, Exome sequencing, Genetic testing, Genetics, medicine.diagnostic_test, business.industry, Prognosis, medicine.disease, HNF1B, HNF1A, Phenotype, 030104 developmental biology, Diabetes Mellitus, Type 2, Mutation, Pediatrics, Perinatology and Child Health, Female, Age of onset, business, Biomarkers, Follow-Up Studies |
| الوصف: | Objectives There have been few large-scale studies utilizing exome sequencing for genetically undiagnosed maturity onset diabetes of the young (MODY), a monogenic form of diabetes that is under-recognized. We describe a cohort of 160 individuals with suspected monogenic diabetes who were genetically assessed for mutations in genes known to cause MODY. Methods We used a tiered testing approach focusing initially on GCK and HNF1A and then expanding to exome sequencing for those individuals without identified mutations in GCK or HNF1A. The average age of onset of hyperglycemia or diabetes diagnosis was 19 years (median 14 years) with an average HbA1C of 7.1%. Results Sixty (37.5%) probands had heterozygous likely pathogenic/pathogenic variants in one of the MODY genes, 90% of which were in GCK or HNF1A. Less frequently, mutations were identified in PDX1, HNF4A, HNF1B, and KCNJ11. For those probands with available family members, 100% of the variants segregated with diabetes in the family. Cascade genetic testing in families identified 75 additional family members with a familial MODY mutation. Conclusions Our study is one of the largest and most ethnically diverse studies using exome sequencing to assess MODY genes. Tiered testing is an effective strategy to genetically diagnose atypical diabetes, and familial cascade genetic testing identified on average one additional family member with monogenic diabetes for each mutation identified in a proband. |
| تدمد: | 2191-0251 0334-018X 2020-0501 |
| DOI: | 10.1515/jpem-2020-0501 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc780e6b488e21cf2fc0f021ecc0e9b2 https://doi.org/10.1515/jpem-2020-0501 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dc780e6b488e21cf2fc0f021ecc0e9b2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21910251 0334018X 20200501 |
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| DOI: | 10.1515/jpem-2020-0501 |