Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects
Summary: Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such as MYH7, TPM1, and TNNI3 that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopath...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | HGG Advances |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247723000453 |
| _version_ | 1827907476612186112 |
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| author | Jessica X. Chong Matthew Carter Childers Colby T. Marvin Anthony J. Marcello Hernan Gonorazky Lili-Naz Hazrati James J. Dowling Fatema Al Amrani Yasemin Alanay Yolanda Nieto Miguel Á Marín Gabriel Arthur S. Aylsworth Kati J. Buckingham Kathryn M. Shively Olivia Sommers Kailyn Anderson Michael Regnier Michael J. Bamshad |
| author_facet | Jessica X. Chong Matthew Carter Childers Colby T. Marvin Anthony J. Marcello Hernan Gonorazky Lili-Naz Hazrati James J. Dowling Fatema Al Amrani Yasemin Alanay Yolanda Nieto Miguel Á Marín Gabriel Arthur S. Aylsworth Kati J. Buckingham Kathryn M. Shively Olivia Sommers Kailyn Anderson Michael Regnier Michael J. Bamshad |
| author_sort | Jessica X. Chong |
| collection | DOAJ |
| description | Summary: Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such as MYH7, TPM1, and TNNI3 that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In contrast, pathogenic variants in homologous genes such as MYH2, TPM2, and TNNI2 that encode parts of the skeletal muscle sarcomere cause muscle diseases affecting skeletal muscle, such as distal arthrogryposis (DA) syndromes and skeletal myopathies. To date, there have been few reports of genes (e.g., MYH7) encoding sarcomeric proteins in which the same pathogenic variant affects skeletal and cardiac muscle. Moreover, none of the known genes underlying DA have been found to contain pathogenic variants that also cause cardiac abnormalities. We report five families with DA because of heterozygous missense variants in the gene actin, alpha, cardiac muscle 1 (ACTC1). ACTC1 encodes a highly conserved actin that binds to myosin in cardiac and skeletal muscle. Pathogenic variants in ACTC1 have been found previously to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. Our discovery delineates a new DA condition because of variants in ACTC1 and suggests that some functions of ACTC1 are shared in cardiac and skeletal muscle. |
| first_indexed | 2024-03-13T01:09:23Z |
| format | Article |
| id | doaj.art-08f67d5e060d475c83319e61695d173d |
| institution | Directory Open Access Journal |
| issn | 2666-2477 |
| language | English |
| last_indexed | 2024-03-13T01:09:23Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj.art-08f67d5e060d475c83319e61695d173d2023-07-06T04:18:20ZengElsevierHGG Advances2666-24772023-07-0143100213Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defectsJessica X. Chong0Matthew Carter Childers1Colby T. Marvin2Anthony J. Marcello3Hernan Gonorazky4Lili-Naz Hazrati5James J. Dowling6Fatema Al Amrani7Yasemin Alanay8Yolanda Nieto9Miguel Á Marín Gabriel10Arthur S. Aylsworth11Kati J. Buckingham12Kathryn M. Shively13Olivia Sommers14Kailyn Anderson15Michael Regnier16Michael J. Bamshad17Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Brotman-Baty Institute, Seattle, WA 98195, USADepartment of Bioengineering, University of Washington, Seattle, WA 98195, USA; University of Washington Center for Translational Muscle Research, Seattle, WA 98195, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USADivision of Neurology, The Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaDepartment of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, CanadaDivision of Neurology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Departments of Paediatrics and Molecular Genetics, University of Toronto, Toronto, ON M5G 0A4, CanadaDivision of Neurology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Division of Neurology, Department of Pediatrics, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Sultanate of OmanDivision of Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, TurkeyDepartment of Basic Bio-Medical Sciences, European University of Madrid, Madrid, SpainDepartment of Pediatrics, Puerta de Hierro-Majadahonda University Hospital, 28221 Madrid, SpainDepartments of Pediatrics and Genetics, University of North Carolina, Chapel Hill, NC 27599, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USADepartment of Bioengineering, University of Washington, Seattle, WA 98195, USA; University of Washington Center for Translational Muscle Research, Seattle, WA 98195, USADivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Brotman-Baty Institute, Seattle, WA 98195, USA; University of Washington Center for Translational Muscle Research, Seattle, WA 98195, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Seattle Children’s Hospital, Seattle, WA 98105, USA; Corresponding authorSummary: Contraction of the human sarcomere is the result of interactions between myosin cross-bridges and actin filaments. Pathogenic variants in genes such as MYH7, TPM1, and TNNI3 that encode parts of the cardiac sarcomere cause muscle diseases that affect the heart, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In contrast, pathogenic variants in homologous genes such as MYH2, TPM2, and TNNI2 that encode parts of the skeletal muscle sarcomere cause muscle diseases affecting skeletal muscle, such as distal arthrogryposis (DA) syndromes and skeletal myopathies. To date, there have been few reports of genes (e.g., MYH7) encoding sarcomeric proteins in which the same pathogenic variant affects skeletal and cardiac muscle. Moreover, none of the known genes underlying DA have been found to contain pathogenic variants that also cause cardiac abnormalities. We report five families with DA because of heterozygous missense variants in the gene actin, alpha, cardiac muscle 1 (ACTC1). ACTC1 encodes a highly conserved actin that binds to myosin in cardiac and skeletal muscle. Pathogenic variants in ACTC1 have been found previously to underlie atrial septal defect, dilated cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction. Our discovery delineates a new DA condition because of variants in ACTC1 and suggests that some functions of ACTC1 are shared in cardiac and skeletal muscle.http://www.sciencedirect.com/science/article/pii/S2666247723000453exome sequencingMendelian diseaseMendelian disordercongenital contracturesdistal arthrogryposiscardiomyopathy |
| spellingShingle | Jessica X. Chong Matthew Carter Childers Colby T. Marvin Anthony J. Marcello Hernan Gonorazky Lili-Naz Hazrati James J. Dowling Fatema Al Amrani Yasemin Alanay Yolanda Nieto Miguel Á Marín Gabriel Arthur S. Aylsworth Kati J. Buckingham Kathryn M. Shively Olivia Sommers Kailyn Anderson Michael Regnier Michael J. Bamshad Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects HGG Advances exome sequencing Mendelian disease Mendelian disorder congenital contractures distal arthrogryposis cardiomyopathy |
| title | Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects |
| title_full | Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects |
| title_fullStr | Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects |
| title_full_unstemmed | Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects |
| title_short | Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects |
| title_sort | variants in actc1 underlie distal arthrogryposis accompanied by congenital heart defects |
| topic | exome sequencing Mendelian disease Mendelian disorder congenital contractures distal arthrogryposis cardiomyopathy |
| url | http://www.sciencedirect.com/science/article/pii/S2666247723000453 |
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