Discordant clinical features of identical hypertrophic cardiomyopathy twins.
Proc Natl Acad Sci U S A
; 118(10)2021 03 09.
Article
en En
| MEDLINE
| ID: mdl-33658374
ABSTRACT
Hypertrophic cardiomyopathy (HCM) is a disease of heart muscle, which affects â¼1 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Gemelos Monocigóticos
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Cardiomiopatía Hipertrófica
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Ecocardiografía
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Epigénesis Genética
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Ventrículos Cardíacos
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Proteínas Musculares
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Adolescent
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Adult
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2021
Tipo del documento:
Article