Novel ACTA1 mutation causes late-presenting nemaline myopathy with unusual dark cores.
Neuromuscul Disord
; 31(2): 139-148, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33384202
ABSTRACT
ACTA1 gene encodes the skeletal muscle alpha-actin, the core of thin filaments of the sarcomere. ACTA1 mutations are responsible of several muscle disorders including nemaline, cores, actin aggregate myopathies and fiber-type disproportion. We report clinical, muscle imaging, histopatological and genetic data of an Italian family carrying a novel ACTA1 mutation. All affected members showed a late-presenting, diffuse muscle weakness with sternocleidomastoideus and temporalis atrophy. Mild dysmorphic features were also detected. The most affected muscles by muscle MRI were rectus abdominis, gluteus minimus, vastus intermedius and both gastrocnemii. Muscle biopsy showed the presence of nemaline bodies with several unusual dark areas at Gomori Trichrome, corresponding to unstructured cores with abundant electrodense material by electron microscopy. The molecular analysis revealed missense variant c.148G>A; p.(Gly50Ser) in the exon 3 of ACTA1, segregating with affected members in the family. We performed a functional essay of fibre contractility showing a higher pCa50 (a measure of the calcium sensitivity of force) of type 1 fibers compared to control subjects' type 1 muscle fibers. Our findings expand the clinico-pathological spectrum of ACTA1-related congenital myopathies and the genetic spectrum of core-rod myopathies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Actinas
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Miopatias da Nemalina
/
Mutação
Tipo de estudo:
Etiology_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Neuromuscul Disord
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM