Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myopathies with rimmed 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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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 found and needs further study.</p>

Familial and sporadic distal myopathy with rimmed vacuoles: comparison of the clinical, pathological, laboratory test and follow-up data / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the clinical, pathological, laboratory test and follow-up data between familial and sporadic patients with distal myopathy with rimmed vacuoles (DMRV) and discuss the characteristics of this disorder in Chinese population.</p><p><b>METHODS</b>The clinical and pathological features, laboratory data and follow-up results of 33 sporadic and 4 familial cases of pathologically confirmed DMRV were summarized and compared retrospectively.</p><p><b>RESULTS</b>The patients age, onset age, or disease duration showed no significant difference between sporadic and familial cases; the onset pattern and affected muscle groups were also similar, but the sporadic cases showed more frequent dysmorphic features than the familial cases. The patients showed mild to moderate elevation of the muscle enzymes by one to three folds, and the familial patients had more significant elevation than the sporadic ones. No correlation was found between the disease duration and the level of muscle enzymes. The pathological findings were similar between the cases, and Gomori staining showed rimmed vacuoles and inclusion bodies without inflammatory cell infiltration. Follow-up results of 29 cases showed no significant difference between the two groups. The disease was slowly progressive and severely affected the quality of life of the patients, but did not produce obvious effect on the life expectancy.</p><p><b>CONCLUSION</b>The clinical, pathological and laboratory data of Chinese DMRV patients are basically similar to those of Japanese cases. Sporadic cases tend to show more dysmorphic features than the familial ones, and occasional sporadic cases have early disease onset in early childhood.</p>

GNE gene mutation analysis in 5 patients with distal myopathy with rimmed vacuoles / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate GNE gene mutations in 5 Chinese patients with distal myopathy with rimmed vacuoles (DMRV).</p><p><b>METHODS</b>Five patients with typical clinical and pathological features of DMRV were studied. All the 11 coding exons and the flanking intron sequences of GNE gene were amplified by PCR and sequenced. Four family members of case 5 were also examined for GNE gene mutations.</p><p><b>RESULTS</b>All the patients were identified to have different GNE gene mutations: Cases 1-4 had complex heterozygous mutations and case 5 had homozygous mutation. Six reported mutations had been identified, including 1 nonsense mutation (p.R8X) and 5 missense mutations (p.D176V, p.I298T, p.A591T, P.A631V, and p.V696M). A novel mutation (c.317T>C, p.I106T) was identified in case 2.</p><p><b>CONCLUSION</b>This is the first report of p.R8X, p.I298T, p.A591T and p.V696M mutations in GNE gene in Chinese population, and a novel mutation p.I106T was identified. These findings further expand the clinical and genetic spectrum of DMRV in China.</p>