Fig 2: Clinical and histopathological features in our patients. (A) Pedigree of our family with ACTN2 variant. Circle: females; square: males; open symbol: unaffected; filled symbol: affected; arrow: proband. The “+” symbols indicate the presence and the “‐” symbols indicate the absence of the mutation. (B) Marked atrophy of the proband's legs. (C and D) MRI imaging of the proband. Extensive fatty infiltration (white arrow) and partial edema (yellow arrow) on the left leg. (E) Severe upper limbs atrophy in the father (I‐2). (F) Contractures in hands of the father (I‐2). (G) Histological findings in the proband. Internal nuclei (yellow arrow) in H&E staining. Multiple well‐delimited cores (yellow arrow) observed in NADH‐TR, SDH, and COX reactions. ATPase reaction (pH =4.6 and 9.4, respectively) showed both type I and type II fibers‐grouping and atrophy predominantly in type I fibers; Scale bar, 50 μm

Fig 3: Genetic findings in patients and pathogenic variants in ACTN2. (A) Sequencing chromatogram of the presence of mutation c.2504delT, p. Phe835Serfs*66 in the proband (upper), and absence in the control (lower). (B) The Phe835 residue is highly conserved in different species. (C) Schematic representation of ACTN2 and summary of reported pathogenic variants. Red: novel variants; Blue: actininopathy‐related variants; Green: MsCD‐related variants; Black: HCM, DCM and/or other cardiac abnormalities‐related variants