A recurrent ACTA1 amino acid change in mosaic form causes milder asymmetric myopathy

Vilma Lotta Lehtokari, Lydia Sagath, Mark Davis, Desiree Ho, Kirsi Kiiski, Kaisa Kettunen, Matthew Demczko, Riki Stein, Matteo Vatta, Thomas L. Winder, Adi Shohet, Naama Orenstein, Peter Krcho, Peter Bohuš, Sanna Huovinen, Bjarne Udd, Katarina Pelin, Nigel G. Laing, Carina Wallgren-Pettersson

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

1 Sitaatiot (Scopus)
5 Lataukset (Pure)

Abstrakti

We describe three patients with asymmetric congenital myopathy without definite nemaline bodies and one patient with severe nemaline myopathy. In all four patients, the phenotype had been caused by pathogenic missense variants in ACTA1 leading to the same amino acid change, p.(Gly247Arg). The three patients with milder myopathy were mosaic for their variants. In contrast, in the severely affected patient, the missense variant was present in a de novo, constitutional form. The grade of mosaicism in the three mosaic patients ranged between 20 % and 40 %. We speculate that the milder clinical and histological manifestations of the same ACTA1 variant in the patients with mosaicism reflect the lower abundance of mutant actin in their muscle tissue. Similarly, the asymmetry of body growth and muscle weakness may be a consequence of the affected cells being unevenly distributed. The partial improvement in muscle strength with age in patients with mosaicism might be due to an increased proportion over time of nuclei carrying and expressing two normal alleles.

AlkuperäiskieliEnglanti
Sivut32-40
Sivumäärä9
JulkaisuNEUROMUSCULAR DISORDERS
Vuosikerta34
Varhainen verkossa julkaisun päivämäärämarrask. 2023
DOI - pysyväislinkit
TilaJulkaistu - tammik. 2024
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

  • Jufo-taso 1

!!ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)

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