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

Abstract

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.

Abstract

Actin, alpha, skeletal muscle 1 (ACTA1) is one of the causative genes of nemaline myopathy (NM) and congenital fiber‐type disproportion (CFTD). Herein, we report a 10‐year‐old boy presented with CFTD and dilated cardiomyopathy (DCM), who has a novel de novo mutation, c.980T>A, p.(Met327Lys), in ACTA1. Met327Lys‐transfected cells showed few aggregations and numerous apoptotic cells. This result supports the pathogenicity of the mutation and can be implicated as one of the histopathological features associated with CFTD, as in NM.