Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Immunology Year : 2021

Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease

(1) , (1) , (2) , (3) , (2) , (3) , (2) , (2) , (2) , (2) , (2) , (2) , (2) , (1) , (1) , (1) , (2) , (2) , (4) , (4) , (5) , (6) , (7) , (5) , (4) , (2) , (5) , (6) , (8) , (1)
1
2
3
4
5
6
7
8
Laurent Abel

Abstract

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy. Methods We used whole exome sequencing to study nuclear families containing multiple cases of Chagas disease. We searched for rare pathogenic variants shared by all family members with CCC but absent in infected ASY siblings and in unrelated ASY. Results We identified heterozygous, pathogenic variants linked to CCC in all tested families on 22 distinct genes, from which 20 were mitochondrial or inflammation-relatedmost of the latter involved in proinflammatory cytokine production. Significantly, Edecio Cunha-Neto and Christophe Chevillard contributed equally to this work.
Fichier principal
Vignette du fichier
Ouarhache2021_Article_RarePathogenicVariantsInMitoch.pdf (847.62 Ko) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

hal-03162042 , version 1 (08-03-2021)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Maryem Ouarhache, Sandrine Marquet, Amanda Farage Frade, Ariela Mota Ferreira, Barbara Ianni, et al.. Rare Pathogenic Variants in Mitochondrial and Inflammation-Associated Genes May Lead to Inflammatory Cardiomyopathy in Chagas Disease. Journal of Clinical Immunology, 2021, ⟨10.1007/s10875-021-01000-y⟩. ⟨hal-03162042⟩
54 View
71 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More