Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/16557
Title: A novel mechanism for human cardiac Ankyrin-B syndrome due to reciprocal chromosomal translocation
Austin Authors: Huq, Aamira J;Pertile, MD;Davis, AM;Landon, H;James, PA;Kline, CF;Vohra, J;Mohler, PJ;Delatycki, Martin B 
Affiliation: Department of Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia
Victorian Clinical Genetics Services, Melbourne, Victoria, Australia
Department of Cardiology, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Genetic Medicine, Royal Melbourne Hospital, Melbourne, Victoria, Australia
Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Dorothy M. Davis Heart and Lung Research Institute; Departments of Physiology & Cell Biology and Internal Medicine; Ohio State University Wexner Medical Center, Columbus, OH, USA
Bruce Lefroy Centre, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia
Issue Date: Jun-2017
metadata.dc.date: 2016-11-16
Publication information: Heart, Lung and Circulation 2017; 26(6): 612-618
Abstract: 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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/16557
DOI: 10.1016/j.hlc.2016.09.013
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/27916589
Type: Journal Article
Subjects: ANK2
Ankyrin-B
Ankyrin-B syndrome
Cardiac arrhythmia
Chromosome 4 translocation
Long QT syndrome type 4
Appears in Collections:Journal articles

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