دورية أكاديمية
Chinese carrier of the HNF1A p.Gln444fs variant exhibits enhanced response to sulfonylureas
| العنوان: | Chinese carrier of the HNF1A p.Gln444fs variant exhibits enhanced response to sulfonylureas |
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| المؤلفون: | Xiufang Wang, Wenzhuo Cheng, Zhongjing Wang, Chao Liu, Aiping Deng, Juyi Li |
| المصدر: | Heliyon, Vol 10, Iss 15, Pp e35112- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science (General) LCC:Social sciences (General) |
| مصطلحات موضوعية: | HNF1A, MODY3, Monogenic diabetes, Precision therapy, Whole-exome sequencing, Science (General), Q1-390, Social sciences (General), H1-99 |
| الوصف: | Background: We assessed the response to sulfonylureas and the functional characteristics of HNF1A mutations in patients with maturity-onset diabetes of the young type 3 (MODY3). Methods: We recruited a family with suspected MODY in this study, and gene sequencing (whole-exome sequencing) was used to screen germline mutations. Luciferase reporter assays were used to evaluate the activity of the mutated genes. Results: Heterozygous HNF1A variant (NM_000545.8:c.1330_1331del, p.Gln444fs) was identified in the proband and was not found in his father, grandmother, and nonrelated healthy controls. The mutant protein had 552 amino acids, 110 fewer than the wild type protein. Furthermore, the amino acid sequence was completely different between the mutant protein and the wild type protein starting from the 444th amino acid. Luciferase reporter assays revealed that the variant had impaired HNF4A promoter–regulation activity. The patient did not achieve good hypoglycemic effects during long-term treatment with insulin and metformin. The effect of hypoglycemic treatment was highly significant after the addition of sulfonylurea drugs. Conclusions: The HNF1A p.Gln444fs variant associated with MODY3, and most likely a truncated protein, impaired HNF1A transcriptional activity. The variant carrier experienced an enhanced response to sulfonylureas. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-8440 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2405844024111437; https://doaj.org/toc/2405-8440 |
| DOI: | 10.1016/j.heliyon.2024.e35112 |
| URL الوصول: | https://doaj.org/article/97c837c96c4f4c959a6592f9b4d45558 |
| رقم الأكسشن: | edsdoj.97c837c96c4f4c959a6592f9b4d45558 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24058440 |
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| DOI: | 10.1016/j.heliyon.2024.e35112 |