A case of congenital fiber-type disproportion syndrome presenting dilated cardiomyopathy with ACTA1 mutation.

Autor: Matsumoto A; Department of Pediatrics, Jichi Medical University, Tochigi, Japan.; Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Tsuda H; Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Furui S; Department of Pediatrics, Jichi Medical University, Tochigi, Japan., Kawada-Nagashima M; Department of Pediatrics, Jichi Medical University, Tochigi, Japan., Anzai T; Department of Pediatrics, Jichi Medical University, Tochigi, Japan., Seki M; Department of Pediatrics, Jichi Medical University, Tochigi, Japan., Watanabe K; Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Muramatsu K; Department of Pediatrics, Jichi Medical University, Tochigi, Japan., Osaka H; Department of Pediatrics, Jichi Medical University, Tochigi, Japan., Iwamoto S; Division of Human Genetics, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan., Nishino I; Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan., Yamagata T; Department of Pediatrics, Jichi Medical University, Tochigi, Japan.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2022 Sep; Vol. 10 (9), pp. e2008. Date of Electronic Publication: 2022 Jun 27.
DOI: 10.1002/mgg3.2008
Abstrakt: Background: Actin, alpha, skeletal muscle 1 (ACTA1) is one of the causative genes of nemaline myopathy (NM) and congenital fiber-type disproportion (CFTD). CFTD is characterized by type 1 fiber atrophy and distinguished from NM in the absence of rods. Eight patients with CFTD, including one patient with dilated cardiomyopathy (DCM), have previously been reported. Herein, we report the case of a 10-year-old boy presenting with CFTD and DCM.
Methods: We performed exome sequencing and analyzed the effect of Met327Lys mutations on cultured C2C12 muscle cells compared with that seen in the wild type (WT, ACTA1) and previously identified Asp294Val mutations associated with a severe phenotype of CFTD without cardiomyopathy.
Results: Exome sequencing revealed a de novo mutation, c.980 T > A, p.(Met327Lys), in ACTA1 (NM_001100.4). C2C12 cells transfected with the WT plasmid expressed ACTA1 in the nucleus and cytoplasm. Cells with the Asp294Val mutant showed needle-like structures in the cytoplasm, whereas the expression of the Met327Lys mutant resulted in few aggregations but many apoptotic cells.
Conclusion: Apoptosis induced in Met327Lys-transfected muscle cells supports the pathogenicity of the mutation and can be implicated as one of the histopathological features associated with CFTD, as in NM.
(© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje