GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.786705/full |
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| author | Krista Heliö Mikko I. Mäyränpää Inka Saarinen Saija Ahonen Heidi Junnila Johanna Tommiska Sini Weckström Miia Holmström Mia Toivonen Kjell Nikus 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 |
| author_facet | Krista Heliö Mikko I. Mäyränpää Inka Saarinen Saija Ahonen Heidi Junnila Johanna Tommiska Sini Weckström Miia Holmström Mia Toivonen Kjell Nikus 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 |
| author_sort | Krista Heliö |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T04:37:44Z |
| format | Article |
| id | doaj.art-1aa59acef3044845853059e28698c9e3 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T04:37:44Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-1aa59acef3044845853059e28698c9e32022-12-21T20:35:43ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-11-011210.3389/fgene.2021.786705786705GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated CardiomyopathyKrista Heliö0Mikko I. Mäyränpää1Inka Saarinen2Saija Ahonen3Heidi Junnila4Johanna Tommiska5Sini Weckström6Miia Holmström7Mia Toivonen8Kjell Nikus9Kjell Nikus10Julie Hathaway11Pauli Siivonen12Mikko Muona13Johanna Sistonen14Pertteli Salmenperä15Massimiliano Gentile16Jussi Paananen17Samuel Myllykangas18Tero-Pekka Alastalo19Tiina Heliö20Juha Koskenvuo21Heart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandDepartment of Pathology, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandHeart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandDepartment of Radiology, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandFaculty of Medicine and Health Technology, Tampere University, Tampere, FinlandHeart Center, Tampere University Hospital, Tampere, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandHeart and Lung Center, Helsinki University Hospital and University of Helsinki, Helsinki, FinlandBlueprint Genetics, A Quest Diagnostics Company, Espoo, FinlandBackground: 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.https://www.frontiersin.org/articles/10.3389/fgene.2021.786705/fullGCOM1MYZAPdilated cardiomyopathyautosomal recessivecardiomyopathy |
| spellingShingle | Krista Heliö Mikko I. Mäyränpää Inka Saarinen Saija Ahonen Heidi Junnila Johanna Tommiska Sini Weckström Miia Holmström Mia Toivonen Kjell Nikus 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 GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy Frontiers in Genetics GCOM1 MYZAP dilated cardiomyopathy autosomal recessive cardiomyopathy |
| title | GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy |
| title_full | GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy |
| title_fullStr | GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy |
| title_full_unstemmed | GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy |
| title_short | GRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy |
| title_sort | grinl1a complex transcription unit containing gcom1 myzap and polr2m genes associates with fully penetrant recessive dilated cardiomyopathy |
| topic | GCOM1 MYZAP dilated cardiomyopathy autosomal recessive cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.786705/full |
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