دورية أكاديمية
Dysgenesis and Dysfunction of the Pancreas and Pituitary Due to FOXA2 Gene Defects.
| العنوان: | Dysgenesis and Dysfunction of the Pancreas and Pituitary Due to FOXA2 Gene Defects. |
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| المؤلفون: | Kaygusuz SB; Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey., Arslan Ates E; Department of Medical Genetics, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey., Vignola ML; Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, UK., Volkan B; Department of Pediatric Gastroenterology, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey., Geckinli BB; Department of Medical Genetics, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey., Turan S; Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey., Bereket A; Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey., Gaston-Massuet C; Centre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, Charterhouse Square, London, UK., Guran T; Department of Pediatric Endocrinology and Diabetes, Marmara University School of Medicine, Ustkaynarca/Pendik, Istanbul, Turkey. |
| المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2021 Sep 27; Vol. 106 (10), pp. e4142-e4154. |
| نوع المنشور: | Case Reports; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
| مواضيع طبية MeSH: | Diabetes Mellitus/*congenital , Hepatocyte Nuclear Factor 3-beta/*genetics , Hypopituitarism/*congenital , Pancreas/*abnormalities , Pituitary Gland/*abnormalities, Codon, Nonsense ; Glucose Transporter Type 2/genetics ; Humans ; Infant ; Male ; Syndrome ; Transcription Factors/genetics ; Transcriptional Activation |
| مستخلص: | Context: Developmental disorders of the pituitary gland leading to congenital hypopituitarism can either be isolated or associated with extrapituitary abnormalities (syndromic hypopituitarism). A large number of syndromic hypopituitarism cases are linked to mutations in transcription factors. The forkhead box A2 (FOXA2) is a transcription factor that plays a key role in the central nervous system, foregut, and pancreatic development. Objective: This work aims to characterize 2 patients with syndromic hypopituitarism due to FOXA2 gene defects. Results: We report a novel heterozygous nonsense c.616C > T(p.Q206X) variant that leads to a truncated protein that lacks part of the DNA-binding domain of FOXA2, resulting in impaired transcriptional activation of the glucose transporter type 2 (GLUT2)-luciferase reporter. The patient is the sixth patient described in the literature with a FOXA2 mutation, and the first patient exhibiting pancreatic hypoplasia. We also report a second patient with a novel de novo 8.53 Mb deletion of 20p11.2 that encompasses FOXA2, who developed diabetes mellitus that responded to sulfonylurea treatment. Conclusion: Our 2 cases broaden the molecular and clinical spectrum of FOXA2-related disease, reporting the first nonsense mutation and the first case of pancreatic dysgenesis. (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) |
| فهرسة مساهمة: | Keywords: FOXA2; abdominal heterotaxy; congenital hypopituitarism; diabetes; hyperinsulinism; pancreatic hypoplasia |
| المشرفين على المادة: | 0 (Codon, Nonsense) 0 (FOXA2 protein, human) 0 (Glucose Transporter Type 2) 0 (SLC2A2 protein, human) 0 (Transcription Factors) 135845-92-0 (Hepatocyte Nuclear Factor 3-beta) |
| تواريخ الأحداث: | Date Created: 20210517 Date Completed: 20211116 Latest Revision: 20211116 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1210/clinem/dgab352 |
| PMID: | 33999151 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-7197 |
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| DOI: | 10.1210/clinem/dgab352 |