Mutation update for the ACTN2 gene
Ranta-aho, Johanna (University of Helsinki)
Olive, Montse (Institut d'Investigació Biomèdica Sant Pau)
Vandroux, Marie (Université de Strasbourg)
Roticiani, Giorgia (Folkhälsan Research Center)
Dominguez, Cristina (Instituto de Salud Carlos III)
Johari, Mridul (University of Helsinki)
Torella, Annalaura (University of Campania 'Luigi Vanvitelli')
Böhm, Johann (Université de Strasbourg)
Turon, Janina (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Nigro, Vincenzo (University of Campania 'Luigi Vanvitelli')
Hackman, Peter (University of Helsinki)
Laporte, Jocelyn (Université de Strasbourg)
Udd, Bjarne (Vaasa Central Hospital)
Savarese, Marco (University of Helsinki)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	ACTN2 encodes alpha-actinin-2, a protein expressed in human cardiac and skeletal muscle. The protein, located in the sarcomere Z-disk, functions as a link between the anti-parallel actin filaments. This important structural protein also binds N-terminal titins, and thus contributes to sarcomere stability. Previously, ACTN2 mutations have been solely associated with cardiomyopathy, without skeletal muscle disease. Recently, however, ACTN2 mutations have been associated with novel congenital and distal myopathy. Previously reported variants are in varying locations across the gene, but the potential clustering effect of pathogenic locations is not clearly understood. Further, the genotype-phenotype correlations of these variants remain unclear. Here we review the previously reported ACTN2-related molecular and clinical findings and present an additional variant, c. 1840-2A>T, that further expands the mutation and phenotypic spectrum. Our results show a growing body of clinical, genetic, and functional evidence, which underlines the central role of ACTN2 in the muscle tissue and myopathy. However, limited segregation and functional data are available to support the pathogenicity of most previously reported missense variants and clear-cut genotype-phenotype correlations are currently only demonstrated for some ACTN2-related myopathies.
Ajuts:	Instituto de Salud Carlos III PI21/01621
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	ACTN2 ; Alpha-actinin-2 ; Cardiomyopathy ; Congenital myopathy ; Distal myopathy
Publicat a:	Human mutation, Vol. 43 Núm. 12 (december 2022) , p. 1745-1756, ISSN 1098-1004

DOI: 10.1002/humu.24470
PMID: 36116040

12 p, 1.3 MB

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