دورية أكاديمية
أعرض في EDS

Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism.

التفاصيل البيبلوغرافية
العنوان: Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism.
المؤلفون: Lee CT; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan., Tsai WH; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chang CC; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chen PC; Department of Physiology, National Cheng-Kung University, Tainan, Taiwan., Fann CS; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chang HK; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Liu SY; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan., Wu MZ; Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan., Chiu PC; Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan., Hsu WM; Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan., Yang WS; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan., Lai LP; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan., Tsai WY; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan., Yang SB; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Chen PL; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei, Taiwan.; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
المصدر: Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Nov 16; Vol. 14, pp. 1283907. Date of Electronic Publication: 2023 Nov 16 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101555782 Publication Model: eCollection Cited Medium: Print ISSN: 1664-2392 (Print) Linking ISSN: 16642392 NLM ISO Abbreviation: Front Endocrinol (Lausanne) Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Potassium Channels, Inwardly Rectifying*/genetics , Congenital Hyperinsulinism*/drug therapy , Congenital Hyperinsulinism*/genetics, Humans ; Child ; Diazoxide/therapeutic use ; Sulfonylurea Receptors/genetics ; Genetic Association Studies ; Adenosine Triphosphate
مستخلص: Objective: Congenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations.
Methods: We combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes. The allele frequency of the most common variant was estimated by single-nucleotide polymorphism haplotype analysis. The functional effects of the ATP-sensitive potassium (K ATP ) channel variants were assessed using patch clamp recording and Western blot.
Results: Nine of 13 (69%) patients with ten different pathogenic variants (7 in ABCC8 , 2 in KCNJ11 and 1 in GCK ) were identified by the combined sequencing. The variant ABCC8 p.T1042QfsX75 identified in three probands was located in a specific haplotype. Functional study revealed the human SUR1 (hSUR1)-L366F K ATP channels failed to respond to intracellular MgADP and diazoxide while hSUR1-R797Q and hSUR1-R1393C K ATP channels were defective in trafficking. One patient had a de novo dominant mutation in the GCK gene (p.I211F), and WES revealed mosaicism of this variant from another patient.
Conclusion: Pathogenic variants in K ATP channels are the most common underlying cause of diazoxide-unresponsive CHI in the Taiwanese cohort. The p.T1042QfsX75 variant in the ABCC8 gene is highly suggestive of a founder effect. The I211F mutation in the GCK gene and three rare SUR1 variants associated with defective gating (p.L366F) or traffic (p.R797Q and p.R1393C) K ATP channels are also associated with the diazoxide-unresponsive phenotype.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Lee, Tsai, Chang, Chen, Fann, Chang, Liu, Wu, Chiu, Hsu, Yang, Lai, Tsai, Yang and Chen.)
References: J Formos Med Assoc. 2016 May;115(5):306-10. (PMID: 25960244)
Mol Genet Genomic Med. 2015 Jun 29;3(6):526-36. (PMID: 26740944)
Eur J Endocrinol. 2014 Dec;171(6):685-95. (PMID: 25201519)
J Biol Chem. 2013 Jul 19;288(29):20942-20954. (PMID: 23744072)
Blood. 2004 Mar 1;103(5):1937-40. (PMID: 14604959)
Cell Rep. 2019 May 7;27(6):1848-1857.e4. (PMID: 31067468)
Eur J Endocrinol. 2011 Jun;164(6):919-26. (PMID: 21422196)
Eur J Endocrinol. 2013 Mar 15;168(4):557-64. (PMID: 23345197)
NPJ Genom Med. 2021 Feb 11;6(1):10. (PMID: 33574314)
Arch Dis Child Fetal Neonatal Ed. 2000 Mar;82(2):F98-F107. (PMID: 10685981)
J Clin Res Pediatr Endocrinol. 2015 Jun;7(2):151-4. (PMID: 26316440)
J Clin Endocrinol Metab. 2004 Dec;89(12):6224-34. (PMID: 15579781)
Am J Hum Genet. 2007 Aug;81(2):375-82. (PMID: 17668386)
Front Endocrinol (Lausanne). 2022 Jul 07;13:873254. (PMID: 35872984)
J Clin Invest. 2021 Feb 1;131(3):. (PMID: 33529164)
J Biomed Sci. 2014 Aug 30;21:88. (PMID: 25175702)
N Engl J Med. 1999 Apr 15;340(15):1169-75. (PMID: 10202168)
Nat Commun. 2022 May 19;13(1):2770. (PMID: 35589716)
J Clin Res Pediatr Endocrinol. 2019 Jun 18;11(4):400-409. (PMID: 31208162)
Sci Rep. 2017 Oct 16;7(1):13210. (PMID: 29038438)
Proc Natl Acad Sci U S A. 2021 Nov 30;118(48):. (PMID: 34815345)
Biochemistry. 2009 Feb 10;48(5):814-6. (PMID: 19146401)
Endocr J. 2014;61(9):901-10. (PMID: 25008049)
Pediatrics. 2001 Mar;107(3):476-9. (PMID: 11230585)
Diabetes. 2008 Jan;57(1):259-63. (PMID: 17942822)
Science. 1998 Nov 6;282(5391):1141-4. (PMID: 9804555)
Clin Endocrinol (Oxf). 2005 Apr;62(4):458-65. (PMID: 15807877)
Elife. 2017 Jan 16;6:. (PMID: 28092267)
Genet Med. 2015 May;17(5):405-24. (PMID: 25741868)
J Biol Chem. 2001 Sep 21;276(38):35947-52. (PMID: 11457841)
Hum Reprod. 2015 Jul;30(7):1732-42. (PMID: 25924657)
Eur J Pediatr. 2019 Aug;178(8):1161-1169. (PMID: 31218401)
J Clin Invest. 1997 Aug 15;100(4):802-7. (PMID: 9259578)
J Clin Endocrinol Metab. 2013 Feb;98(2):E355-63. (PMID: 23275527)
Pediatr Diabetes. 2020 May;21(3):441-455. (PMID: 31997554)
J Gen Physiol. 2018 May 7;150(5):653-669. (PMID: 29685928)
Channels (Austin). 2017 Nov 2;11(6):636-647. (PMID: 29087246)
Am J Pathol. 2001 Jun;158(6):2177-84. (PMID: 11395395)
Endocrine. 2021 Apr;72(1):116-123. (PMID: 33502730)
J Pharmacol Exp Ther. 2005 Oct;315(1):352-62. (PMID: 16014573)
PLoS One. 2010 Jun 02;5(6):e10918. (PMID: 20532249)
Elife. 2017 Dec 29;6:. (PMID: 29286281)
J Gen Physiol. 1997 Dec;110(6):643-54. (PMID: 9382893)
J Biol Chem. 2022 May;298(5):101904. (PMID: 35398096)
Hum Mol Genet. 2009 Jul 1;18(13):2400-13. (PMID: 19357197)
J Clin Invest. 2005 Aug;115(8):2047-58. (PMID: 16075046)
Diabetes. 2013 May;62(5):1689-96. (PMID: 23274908)
J Clin Endocrinol Metab. 2011 Dec;96(12):3785-93. (PMID: 21956412)
N Engl J Med. 1998 Jan 22;338(4):226-30. (PMID: 9435328)
Eur J Pediatr. 2002 Jan;161(1):37-48. (PMID: 11808879)
فهرسة مساهمة: Keywords: ABCC8; GCK; KATP channel; KCNJ11; congenital hyperinsulinism; founder mutation
المشرفين على المادة: O5CB12L4FN (Diazoxide)
0 (Potassium Channels, Inwardly Rectifying)
0 (Sulfonylurea Receptors)
8L70Q75FXE (Adenosine Triphosphate)
تواريخ الأحداث: Date Created: 20231130 Date Completed: 20231204 Latest Revision: 20240304
رمز التحديث: 20240304
مُعرف محوري في PubMed: PMC10687152
DOI: 10.3389/fendo.2023.1283907
PMID: 38033998
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-2392
DOI:10.3389/fendo.2023.1283907