Ankyrin-B syndrome: enhanced cardiac function balanced by risk of cardiac death and premature senescence.
Here we report the unexpected finding that specific human ANK2 variants represent a new example of balanced human variants. The prevalence of certain ANK2 (encodes ankyrin-B) variants range from 2 percent of European individuals to 8 percent in individuals from West Africa. Ankyrin-B variants associated with severe human arrhythmia phenotypes (eg E1425G, V1516D, R1788W) were rare in the general population. Variants associated with less severe clinical and in vitro phenotypes were unexpectedly common. Studies with the ankyrin-B(+/-) mouse reveal both benefits of enhanced cardiac contractility, as well as costs in earlier senescence and reduced lifespan. Together these findings suggest a constellation of traits that we term "ankyrin-B syndrome", which may contribute to both aging-related disorders and enhanced cardiac function.
Mohler
Peter J
PJ
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America. peter-mohler@uiowa.edu
Healy
Jane A
JA
Xue
Hui
H
Puca
Annibale A
AA
Kline
Crystal F
CF
Allingham
R Rand
RR
Kranias
Evangelia G
EG
Rockman
Howard A
HA
Bennett
Vann
V
D000375:Aging; D000818:Animals; D017487:Ankyrins / Q000235:genetics* / Q000502:physiology*; D016922:Cellular Senescence; D003643:Death; D004452:Echocardiography / Q000379:methods; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D010641:Phenotype; D012306:Risk; D013577:Syndrome
C498994:ANK2 protein, human; C498995:Ank2 protein, mouse; D017487:Ankyrins