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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Frontiers Media S.A.
2021
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oai:doaj.org-article:1aa59acef3044845853059e28698c9e32021-12-01T01:23:25ZGRINL1A Complex Transcription Unit Containing GCOM1, MYZAP, and POLR2M Genes Associates with Fully Penetrant Recessive Dilated Cardiomyopathy1664-802110.3389/fgene.2021.786705https://doaj.org/article/1aa59acef3044845853059e28698c9e32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fgene.2021.786705/fullhttps://doaj.org/toc/1664-8021Background: 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 HeliöMikko I. MäyränpääInka SaarinenSaija AhonenHeidi JunnilaJohanna TommiskaSini WeckströmMiia HolmströmMia ToivonenKjell NikusKjell NikusJulie HathawayPauli SiivonenMikko MuonaJohanna SistonenPertteli SalmenperäMassimiliano GentileJussi PaananenSamuel MyllykangasTero-Pekka AlastaloTiina HeliöJuha KoskenvuoFrontiers Media S.A.articleGCOM1MYZAPdilated cardiomyopathyautosomal recessivecardiomyopathyGeneticsQH426-470ENFrontiers in Genetics, Vol 12 (2021) |
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GCOM1 MYZAP dilated cardiomyopathy autosomal recessive cardiomyopathy Genetics QH426-470 |
| spellingShingle |
GCOM1 MYZAP dilated cardiomyopathy autosomal recessive cardiomyopathy Genetics QH426-470 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
grinl1a complex transcription unit containing gcom1, myzap, and polr2m genes associates with fully penetrant recessive dilated cardiomyopathy |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/1aa59acef3044845853059e28698c9e3 |
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