-
Tytuł:
-
A Novel Mechanism for Human Cardiac Ankyrin-B Syndrome due to Reciprocal Chromosomal Translocation.
-
Autorzy:
-
Huq AJ; Department of Clinical Genetics, Austin Hospital, Melbourne, Vic, Australia; Department of Genetic Medicine, Royal Melbourne Hospital, Melbourne, Vic, Australia. Electronic address: .
Pertile MD; Victorian Clinical Genetics Services, Melbourne, Vic, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Vic, Australia.
Davis AM; Department of Cardiology, Royal Children's Hospital, Melbourne, Vic, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Vic, Australia; Murdoch Childrens Research Institute, Melbourne, Vic, Australia.
Landon H; Dorothy M. Davis Heart and Lung Research Institute; Departments of Physiology & Cell Biology and Internal Medicine; Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
James PA; Department of Genetic Medicine, Royal Melbourne Hospital, Melbourne, Vic, Australia; Department of Pathology, University of Melbourne, Melbourne, Vic, Australia.
Kline CF; Dorothy M. Davis Heart and Lung Research Institute; Departments of Physiology & Cell Biology and Internal Medicine; Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Vohra J; Department of Genetic Medicine, Royal Melbourne Hospital, Melbourne, Vic, Australia; Department of Cardiology, Royal Melbourne Hospital, Melbourne, Vic, Australia.
Mohler PJ; Dorothy M. Davis Heart and Lung Research Institute; Departments of Physiology & Cell Biology and Internal Medicine; Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Delatycki MB; Department of Clinical Genetics, Austin Hospital, Melbourne, Vic, Australia; Victorian Clinical Genetics Services, Melbourne, Vic, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Vic, Australia; Bruce Lefroy Centre, Murdoch Childrens Research Institute, Melbourne, Vic, Australia.
-
Źródło:
-
Heart, lung & circulation [Heart Lung Circ] 2017 Jun; Vol. 26 (6), pp. 612-618. Date of Electronic Publication: 2016 Nov 16.
-
Typ publikacji:
-
Case Reports; Clinical Trial; Journal Article
-
Język:
-
English
-
Imprint Name(s):
-
Publication: : Chatswood, NSW, Australia : Elsevier Australia
Original Publication: Carlton, Vic., Australia : Blackwell Science Asia, c2000-
-
MeSH Terms:
-
Haploinsufficiency*
Translocation, Genetic*
Ankyrins/*genetics
Arrhythmias, Cardiac/*genetics
Chromosomes, Human, Pair 4/*genetics
Chromosomes, Human, Pair 9/*genetics
Abnormalities, Multiple/genetics ; Abnormalities, Multiple/physiopathology ; Adult ; Arrhythmias, Cardiac/physiopathology ; Family ; Female ; Fetal Diseases/genetics ; Fetal Diseases/physiopathology ; Humans ; Male ; Pregnancy
-
References:
-
Genomics. 1991 Aug;10(4):858-66. (PMID: 1833308)
J Biol Chem. 2004 Sep 17;279(38):40185-93. (PMID: 15262991)
J Cell Mol Med. 2009 Nov-Dec;13(11-12):4364-76. (PMID: 19840192)
J Biol Chem. 2014 Feb 21;289(8):5285-95. (PMID: 24394417)
Circ Res. 2010 Aug 20;107(4):457-65. (PMID: 20724725)
Genome Res. 2002 Jun;12(6):996-1006. (PMID: 12045153)
PLoS One. 2007 Oct 17;2(10):e1051. (PMID: 17940615)
Cardiovasc Res. 2009 Mar 1;81(4):742-9. (PMID: 19074823)
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9137-42. (PMID: 15178757)
J Cardiovasc Electrophysiol. 2006 Oct;17(10):1153-9. (PMID: 16800854)
Exp Eye Res. 2009 Jan;88(1):57-64. (PMID: 19007774)
Sci Signal. 2010 Mar 16;3(113):ra19. (PMID: 20234002)
Methodist Debakey Cardiovasc J. 2014 Jan-Mar;10 (1):29-33. (PMID: 24932360)
Nature. 2003 Feb 6;421(6923):587, 589-90. (PMID: 12571577)
Elife. 2014 Dec 23;3:null. (PMID: 25535840)
J Cell Biol. 2014 Dec 22;207 (6):735-52. (PMID: 25533844)
J Clin Invest. 2015 Aug 3;125(8):3087-102. (PMID: 26168218)
PLoS Biol. 2005 Dec;3(12):e423. (PMID: 16292983)
Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16669-74. (PMID: 19805355)
Nature. 2003 Feb 6;421(6923):634-9. (PMID: 12571597)
J Mol Cell Cardiol. 2009 Aug;47(2):203-9. (PMID: 19394342)
Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a003012. (PMID: 20457566)
Heart Lung Circ. 2007;16 Suppl 3:S5-12. (PMID: 17627884)
BJOG. 2013 Apr;120(5):594-606. (PMID: 23332022)
Circulation. 2007 Jan 30;115(4):432-41. (PMID: 17242276)
-
Grant Information:
-
R01 HL114383 United States HL NHLBI NIH HHS; R35 HL135754 United States HL NHLBI NIH HHS; R01 HL083422 United States HL NHLBI NIH HHS; R01 HL084583 United States HL NHLBI NIH HHS; R01 HL134824 United States HL NHLBI NIH HHS
-
Contributed Indexing:
-
Keywords: ANK2; Ankyrin-B; Ankyrin-B syndrome; Cardiac arrhythmia; Chromosome 4 translocation; Long QT syndrome type 4
-
Substance Nomenclature:
-
0 (ANK2 protein, human)
0 (Ankyrins)
-
SCR Disease Name:
-
Cardiac Arrhythmia, Ankyrin-B-Related
-
Entry Date(s):
-
Date Created: 20161206 Date Completed: 20180220 Latest Revision: 20181113
-
Update Code:
-
20240105
-
PubMed Central ID:
-
PMC5413386
-
DOI:
-
10.1016/j.hlc.2016.09.013
-
PMID:
-
27916589
-
Background: Cardiac rhythm abnormalities are a leading cause of morbidity and mortality in developed countries. Loss-of-function variants in the ANK2 gene can cause a variety of cardiac rhythm abnormalities including sinus node dysfunction, atrial fibrillation and ventricular arrhythmias (called the "ankyrin-B syndrome"). ANK2 encodes ankyrin-B, a molecule critical for the membrane targeting of key cardiac ion channels, transporters, and signalling proteins.
Methods and Results: Here, we describe a family with a reciprocal chromosomal translocation between chromosomes 4q25 and 9q26 that transects the ANK2 gene on chromosome 4 resulting in loss-of-function of ankyrin-B. Select family members with ankyrin-B haploinsufficiency due to the translocation displayed clinical features of ankyrin-B syndrome. Furthermore, evaluation of primary lymphoblasts from a carrier of the translocation showed altered levels of ankyrin-B as well as a reduced expression of downstream ankyrin-binding partners.
Conclusions: Thus, our data conclude that, similar to previously described ANK2 loss-of-function "point mutations", large chromosomal translocations resulting in ANK2 haploinsufficiency are sufficient to cause the human cardiac ankyrin-B syndrome. The unexpected ascertainment of ANK2 dysfunction via the discovery of a chromosomal translocation in this family, the determination of the familial phenotype, as well as the complexities in formulating screening and treatment strategies are discussed.
(Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.)