Homozygous TNNI3 frameshift variant in a consanguineous family with lethal infantile dilated cardiomyopathy.
Mol Genet Genomic Med
; 12(6): e2486, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38924380
ABSTRACT
BACKGROUND:
Dilated cardiomyopathy (DCM) is characterized by dilatation of the left ventricle, systolic dysfunction, and normal or reduced thickness of the left ventricular wall. It is a leading cause of heart failure and cardiac death at a young age. Cases with neonatal onset DCM were correlated with severe clinical presentation and poor prognosis. A monogenic molecular etiology accounts for nearly half of cases. FAMILY DESCRIPTION Here, we report a family with three deceased offspring at the age of 1 year old. The autopsy of the first deceased infant revealed a DCM. The second infant presented a DCM phenotype with a severely reduced Left Ventricular Ejection Fraction (LVEF) of 10%. Similarly, the third infant showed a severe DCM phenotype with LVEF of 30% as well, in addition to eccentric mitral insufficiency.RESULTS:
Exome sequencing was performed for the trio (the second deceased infant and her parents). Data analysis following the autosomal dominant and recessive patterns of inheritance was carried out along with a mitochondrial pathways-based analysis. We identified a homozygous frameshift variant in the TNNI3 gene (c.204delG; p.(Arg69AlafsTer8)). This variant has been recently reported in the ClinVar database in association with cardiac phenotypes as pathogenic or likely pathogenic and classified as pathogenic according to ACMG.CONCLUSION:
Genetic counseling was provided for the family and a prenatal diagnosis of choronic villus was proposed in the absence of pre-implantation genetic diagnosis possibilities. Our study expands the case series of early-onset DCM patients with a protein-truncating variant in the TNNI3 gene by reporting three affected infant siblings.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linaje
/
Cardiomiopatía Dilatada
/
Mutación del Sistema de Lectura
/
Consanguinidad
/
Homocigoto
Límite:
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Mol Genet Genomic Med
Año:
2024
Tipo del documento:
Article
País de afiliación:
Túnez