Front Genet. 2021 Nov 25:12:786705. doi: 10.3389/fgene.2021.786705.

Abstract

Background: Familial dilated cardiomyopathy (DCM) is a monogenic disorder typically inherited in an autosomal dominant pattern. We have identified two Finnish families with familial cardiomyopathy that is not explained by a variant in any previously known cardiomyopathy gene. We describe the cardiac phenotype related to homozygous truncating GCOM1 variants.

Methods and results: This study included two probands and their relatives. All the participants are of Finnish ethnicity. Whole-exome sequencing was used to test the probands; bi-directional Sanger sequencing was used to identify the GCOM1 variants in probands’ family members. Clinical evaluation was performed, medical records and death certificates were obtained. Immunohistochemical analysis of myocardial samples was conducted. A homozygous GCOM1 variant was identified altogether in six individuals, all considered to be affected. None of the nine heterozygous family members fulfilled any cardiomyopathy criteria. Heart failure was the leading clinical feature, and the patients may have had a tendency for atrial arrhythmias.

Conclusions: This study demonstrates the significance of GCOM1 variants as a cause of human cardiomyopathy and highlights the importance of searching for new candidate genes when targeted gene panels do not yield a positive outcome.

Krista Heliö, Mikko I Mäyränpää, Inka Saarinen, Saija Ahonen, Heidi Junnila, Johanna Tommiska, Sini Weckström, Miia Holmström, Mia Toivonen, Kjell Nikus, Julie Hathaway, Pauli Siivonen, Mikko Muona, Johanna Sistonen, Pertteli Salmenperä, Massimiliano Gentile, Jussi Paananen, Samuel Myllykangas, Tero-Pekka Alastalo, Tiina Heliö, Juha Koskenvuo

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