Clinical,Pathological,and Genetic Features of Two Chinese Cases with Filamin C Myopathy

To the Editor:Filamin C (FLNC)myopathy is an autosomal dominant inherited myopathy caused by mutations in FLNC.FLNC belongs to the filamin superfamily and cross-links actin filaments to form a network,anchoring membrane protein to the cytoskeleton. Human protein filamins comprise three isoforms encoded by the human genome:filamins A,B,and C.Among these,FLNC is a Z-disk protein encoded by the FLNC gene and is mainly expressed in the skeletal and cardiac muscles.FLNC gene is on chromosome 7q32-q35,containing genomic DNA of about 29.5 kb length and 49 encoding exons.FLNC is an isoform of serine protease expressed primarily in the striated muscle,containing 2725 amino acids, at a molecular weight of 291,000.FLNC protein contains two domains.The amino terminus consists of two ealponin homology domains that together constitute the actin-binding domain (ABD), followed by 24 filamin-type immunoglobulin (Ig-FLMN)repeated domains (rod-overlapping domains),the most carboxy-terminal of which is responsible for dimerization,assembly,and anchor filaments.

Longitudinal profiled plate straightening process based on curvature integral method

Considering the variable cross section thickness of longitudinal profiled plate and the dynamic reductions of straightening rolls,an analytical model combining curvature integral method with linear decreasing straightening scheme was proposed to investigate the longitudinal profiled plate straightening process.Moreover,the calculation flow and solution algorithm of longitudinal profiled plate straightening process were presented.To verify the proposed model,calculated straightening forces were compared with the measured values,and very good agreements were achieved.Then,the reduction,contact angle,reverse bending curvature,residual curvature,straightening force and straightening moment of longitudinal profiled plate in the straightening process were calculated and analyzed,and the calculated results show that the curvature integral method can be used to reveal the mechanism of longitudinal profiled plate straightening.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision： A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles

Background： Myopathies with rimnled vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected. Methods： A clinical study including family history, obstetric, pediatric, and development history was recorded. Clinical examinations including physical examination, electromyography （EMG）, serum creatine kinase （CK）, bone X-rays, and brain magnetic resonance imaging （MRI） were performed in this family. Open muscle biopsies were performed on the proband and his mother. To find the causative gene, the whole-exome sequencing was carried out. Results： Disease onset was from adolescence to adulthood, but the affected patients of the third generation presented an earlier onset and more severe clinical manifestations than the older generations. Clinical features were characterized as dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision. However, not every patient manifested all symptoms. Serum CK was mildly elevated and EMG indicated a myopathic pattern. Brain MRI showed cerebellum and brain stem mildly atrophy. Rimmed vacuoles and inclusion bodies were observed in muscle biopsy. The whole-exome sequencing was performed, but the causative gene has not been found. Conclusions： We reported a novel autosomal dominant myopathy with rimmed vacuoles characterized by dysarthria, dysphagia, external ophthalmoplegia, limb weakness, hypophrenia, deafness, and impaired vision, but the causative gene has not been tbund and needs further study.