Please use this identifier to cite or link to this item:
|Title:||A novel mechanism for human cardiac Ankyrin-B syndrome due to reciprocal chromosomal translocation|
|Authors:||Huq, Aamira J;Pertile, MD;Davis, AM;Landon, H;James, PA;Kline, CF;Vohra, J;Mohler, PJ;Delatycki, Martin B|
|Citation:||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.|
Chromosome 4 translocation
Long QT syndrome type 4
|Appears in Collections:||Journal articles|
Files in This Item:
There are no files associated with this item.
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.