Faculty Collaboration Database

A novel variant of TNNC1 associated with severe dilated cardiomyopathy causing infant mortality and stillbirth: a case of germline mosaicism. J Genet 2023;102

Date

02/24/2023

Pubmed ID

36814108

Scopus ID

2-s2.0-85146032465 (requires institutional sign-in at Scopus site)

Abstract

Pediatric cardiomyopathies (CM) are rare and challenging to diagnose due to the complex and mixed phenotypes. With the advent of next-generation sequencing (NGS), variants in several genes associated with CM have been identified, such as Troponin C (TnC), encoded by the TNNC1 gene. De novo variants in TNNC1 have been associated with different types of CM, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The American College of Medical Genetics and Genomics recently added TNNC1 to their recommended list of genes for reporting secondary findings. In this study, we report a de novo variant, c.100G>C (p.Gly34Arg) in the TNNC1 gene identified in three siblings with a diagnosis of severe DCM causing infant death for one of the siblings and stillbirth in the other two pregnancies. The identification of the same de novo variant in all affected siblings is suggestive of germline mosaicism in this family.

Author List

Udani R, Schilter KF, Tyler RC, Smith BA, Wendtandrae JL, Kappes UP, Scharer G, Lehman A, Steinraths M, Reddi HV

Author

Kala Schilter in the CTSI department at Medical College of Wisconsin - CTSI

MESH terms used to index this publication - Major topics in bold

Cardiomyopathy, Dilated
Female
Humans
Infant Mortality
Infant, Newborn
Mosaicism
Mutation
Pregnancy
Stillbirth
Troponin C