Mutation update for the ACTN2 gene
Por:
Ranta-aho, J, Olive, M, Vandroux, M, Roticiani, G, Dominguez, C, Johari, M, Torella, A, Bohm, J, Turon, J, Nigro, V, Hackman, P, Laporte, J, Udd, B, Savarese, M
Publicada:
13 dic 2022
Ahead of Print:
1 sep 2022
Resumen:
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.
Filiaciones:
Ranta-aho, J:
Folkhasan Res Ctr, Biomed 1,Haartmaninkatu 8, Helsinki 00290, Finland
Univ Helsinki, Dept Med Genet, Med, Helsinki, Finland
Olive, M:
Hosp Santa Creu & Sant Pau, Neuromuscular Dis Unit, Dept Neurol, Barcelona, Spain
Biomed Res Inst St Pau & IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Vandroux, M:
Univ Strasbourg, IGBMC Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France
Roticiani, G:
Folkhasan Res Ctr, Biomed 1,Haartmaninkatu 8, Helsinki 00290, Finland
Dominguez, C:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Res Inst Imas12, Hosp Univ 12 Octubre,Dept Neurol,Neuromuscular Un, Madrid, Spain
Johari, M:
Folkhasan Res Ctr, Biomed 1,Haartmaninkatu 8, Helsinki 00290, Finland
Univ Helsinki, Dept Med Genet, Med, Helsinki, Finland
Torella, A:
Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy
Bohm, J:
Univ Strasbourg, IGBMC Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France
Turon, J:
Hosp Santa Creu & Sant Pau, Neuromuscular Dis Unit, Dept Neurol, Barcelona, Spain
Biomed Res Inst St Pau & IIB St Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Nigro, V:
Univ Campania Luigi Vanvitelli, Dept Precis Med, Naples, Italy
Hackman, P:
Folkhasan Res Ctr, Biomed 1,Haartmaninkatu 8, Helsinki 00290, Finland
Univ Helsinki, Dept Med Genet, Med, Helsinki, Finland
Laporte, J:
Univ Strasbourg, IGBMC Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France
Udd, B:
Folkhasan Res Ctr, Biomed 1,Haartmaninkatu 8, Helsinki 00290, Finland
Univ Helsinki, Dept Med Genet, Med, Helsinki, Finland
Vaasa Cent Hosp, Dept Neurol, Vaasa, Finland
Savarese, M:
Folkhasan Res Ctr, Biomed 1,Haartmaninkatu 8, Helsinki 00290, Finland
Univ Helsinki, Dept Med Genet, Med, Helsinki, Finland
hybrid, All Open Access; Green
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