Variants in ACTC1 underlie distal arthrogryposis accompanied by congenital heart defects.

Autor:	Chong JX; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.; Brotman-Baty Institute, Seattle, WA 98195, USA., Childers MC; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.; University of Washington Center for Translational Muscle Research, Seattle, WA 98195, USA., Marvin CT; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Marcello AJ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Gonorazky H; Division of Neurology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., Hazrati LN; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., Dowling JJ; Division 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, Canada., Al Amrani F; Division 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 Oman., Alanay Y; Division of Pediatric Genetics, Department of Pediatrics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, 34752 Istanbul, Turkey., Nieto Y; Department of Basic Bio-Medical Sciences, European University of Madrid, Madrid, Spain., Gabriel MÁM; Department of Pediatrics, Puerta de Hierro-Majadahonda University Hospital, 28221 Madrid, Spain., Aylsworth AS; Departments of Pediatrics and Genetics, University of North Carolina, Chapel Hill, NC 27599, USA., Buckingham KJ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Shively KM; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Sommers O; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Anderson K; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA., Regnier M; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.; University of Washington Center for Translational Muscle Research, Seattle, WA 98195, USA., Bamshad MJ; Division 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.
Jazyk:	angličtina
Zdroj:	HGG advances [HGG Adv] 2023 Jun 15; Vol. 4 (3), pp. 100213. Date of Electronic Publication: 2023 Jun 15 (Print Publication: 2023).
DOI:	10.1016/j.xhgg.2023.100213
Abstrakt:	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. Competing Interests: M.J.B. and J.X.C. are the Editor-in-Chief and Deputy Editor of HGG Advances, respectively, and were recused from the editorial handling of this manuscript. (© 2023 The Author(s).)
Databáze:	MEDLINE
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