Discordant clinical features of identical hypertrophic cardiomyopathy twins.

Autor:	Repetti GG; Department of Genetics, Harvard Medical School, Boston, MA 02115., Kim Y; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115., Pereira AC; Heart Institute (InCor), University of Sao Paulo Medical School, 05508-060 Sao Paulo, Brazil., Ingles J; Department of Cardiology, Royal Prince Alfred Hospital, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.; Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW 2006, Australia., Russell MW; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109., Lakdawala NK; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115., Ho CY; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115., Day S; Division of Cardiovascular Medicine, Department of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104., Semsarian C; Department of Cardiology, Royal Prince Alfred Hospital, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.; Agnes Ginges Centre for Molecular Cardiology at Centenary Institute, University of Sydney, Sydney, NSW 2006, Australia., McDonough B; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Howard Hughes Medical Institute, Chevy Chase, MD 20815., DePalma SR; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Howard Hughes Medical Institute, Chevy Chase, MD 20815., Quiat D; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Department of Cardiology, Boston Children's Hospital, Boston, MA 02115., Green EM; Maze Therapeutics, South San Francisco, CA 94080., Seidman CE; Department of Genetics, Harvard Medical School, Boston, MA 02115.; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115.; Howard Hughes Medical Institute, Chevy Chase, MD 20815., Seidman JG; Department of Genetics, Harvard Medical School, Boston, MA 02115; seidman@genetics.med.harvard.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Mar 09; Vol. 118 (10).
DOI:	10.1073/pnas.2021717118
Abstrakt:	Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects ∼1 in 500 individuals and is characterized by increased left ventricular wall thickness. While HCM is caused by pathogenic variants in any one of eight sarcomere protein genes, clinical expression varies considerably, even among patients with the same pathogenic variant. To determine whether background genetic variation or environmental factors drive these differences, we studied disease progression in 11 pairs of monozygotic HCM twins. The twin pairs were followed for 5 to 14 y, and left ventricular wall thickness, left atrial diameter, and left ventricular ejection fraction were collected from echocardiograms at various time points. All nine twin pairs with sarcomere protein gene variants and two with unknown disease etiologies had discordant morphologic features of the heart, demonstrating the influence of nonhereditable factors on clinical expression of HCM. Whole genome sequencing analysis of the six monozygotic twins with discordant HCM phenotypes did not reveal notable somatic genetic variants that might explain their clinical differences. Discordant cardiac morphology of identical twins highlights a significant role for epigenetics and environment in HCM disease progression. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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