A novel variant in VMA21 causing adult-onset phenotype of X-linked myopathy with excessive autophagy with cardiac involvement in a Chinese patient

X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive hereditary disorder, characterized by childhood onset weakness of predominantly limb and trunk skeletal muscles due to progressive loss of muscle tissue. Cardiovascular system is clinically spared generally. Here, we report the clinical characteristics, muscle biopsy and genetic findings of one adult-onset individual suffering from XMEA, caused by a novel variant in a Chinese patient. Unusually, the patient developed unexplained hypertension with high left ventricular voltage and cardiac left ventricular hypertrophy at the age of 27. Muscle MRI revealed extensive fat infiltration in the lower extremities involving vastus medialis, vastus lateralis, vastus intermedius, and long head of the biceps femoris, while rectus femoris, gracilis, adductor magnus, semimembranosus, and sartorius muscle relatively preserved. A muscle biopsy indicated numerous cytoplasmic autophagic vacuoles and deposition of complement C5b-9 and also expression of MHC class I. Immunofluorescence staining showed increased immunoreactivity of lysosomal membrane protein LAMP2 and autophagosome protein LC3A/B both localized with cytoplasmic vacuoles, and autophagy carrier protein P62-positive vacuoles accumulated remarkably in the patient's muscle. VMA21 protein levels were lower than controls in skeletal muscle tissue, suggesting a possible pathogenicity related to an alteration of the splicing efficiency in intronic mutation. This is the first report of a Chinese patient with a novel hemizygous intronic c.163 + 3A > G variant in the VMA21 gene, expanding the mutational and phenotypic spectrum of this disease.