TTR variants in patients with dilated cardiomyopathy: An investigation of the DCM Precision Medicine Study.
Genet Med
; 24(7): 1495-1502, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35438637
ABSTRACT
PURPOSE:
The cardiac phenotype of hereditary transthyretin amyloidosis (hTTR) usually presents as a restrictive or hypertrophic cardiomyopathy, and, although rarely observed as dilated cardiomyopathy (DCM), TTR is routinely included in DCM genetic testing panels. However, the prevalence and phenotypes of TTR variants in patients with DCM have not been reported.METHODS:
Exome sequences of 729 probands with idiopathic DCM were analyzed for TTR and 35 DCM genes.RESULTS:
Rare TTR variants were identified in 2 (0.5%; 95% CI = 0.1%-1.8%) of 404 non-Hispanic White DCM probands; neither of them had features of hTTR. In 1 proband, a TTR His110Asn variant and a variant of uncertain significance in DSP were identified, and in the other proband, a TTR Val50Met variant known to cause hTTR and a likely pathogenic variant in FLNC were identified. The TTR Val142Ile variant was identified in 8 (3.0%) non-Hispanic Black probands, comparable with African/African American Genome Aggregation Database controls (OR = 1.01; 95% CI = 0.46-1.99).CONCLUSION:
Among the 729 DCM probands, 2 had rare TTR variants identified without the features of hTTR, and both had other plausible genetic causes of DCM. Moreover, the frequency of TTR Val142Ile was comparable to a control sample. These findings suggest that hTTR variants may have a limited role in patients with DCM without TTR-specific findings.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
/
Neuropatias Amiloides Familiares
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article