1. GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy
- Author
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Heliö, Krista, Mäyränpää, Mikko I., Saarinen, Inka, Ahonen, Saija, Junnila, Heidi, Tommiska, Johanna, Weckström, Sini, Holmström, Miia, Toivonen, Mia, Nikus, Kjell, Hathaway, Julie, Siivonen, Pauli, Muona, Mikko, Sistonen, Johanna, Salmenperä, Pertteli, Gentile, Massimiliano, Paananen, Jussi, Myllykangas, Samuel, Alastalo, Tero-Pekka, Heliö, Tiina, Koskenvuo, Juha, Faculty of Medicine, HUSLAB, Department of Pathology, HUS Heart and Lung Center, HUS Medical Imaging Center, Department of Diagnostics and Therapeutics, Clinicum, Department of Medicine, Tampere University, Clinical Medicine, and TAYS Heart Centre
- Subjects
MYZAP ,GENETICS ,RECEPTOR ,1184 Genetics, developmental biology, physiology ,PROTEIN ,MYOZAP ,autosomal recessive ,ORGANIZATION ,GUIDELINES ,dilated cardiomyopathy ,Molecular Medicine ,GCOM1 ,3111 Biomedicine ,cardiomyopathy ,Genetics (clinical) ,FORM ,Original Research - 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. publishedVersion
- Published
- 2021