Clinical and genetic analysis of a patient with Desminopathy manifesting initially with myalgia after lower limb activity / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic variant of a patient with desminopathy manifesting with atypical symptoms.@*METHODS@#A patient who was admitted to the Department of Neurology of Jing'an District Central Hospital on February 24, 2021 was selected as the study subject. Clinical data, laboratory tests, muscle pathology, muscle magnetic resonance imaging (MRI) and genetic testing of the patient were retrospectively analyzed.@*RESULTS@#The patient had developed myalgia after lower limb activity, and gradually developed asymmetrical muscle weakness and atrophy of the lower limbs. Cardiac examination revealed atrioventricular block and decreased left ventricular diastolic function. Muscle MRI showed that semitendinosus, sartorius, gracilis, fibula, gastronemius and supinator muscles were selectively involved at the early stage. Muscle biopsy confirmed pathological changes of desmin positive myofibrils. Genetic testing revealed that the patient has harbored a c.1024A>G (p.n342d) missense variant in exon 6 of the DES gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS4_moderate+PM2_supporting+PP3_moderate+PP1).@*CONCLUSION@#Desmin disease has a great clinical heterogeneity. Postexercise myalgia of lower limbs is a rare clinical phenotype. For patients harboring the c.1024A>G (p.n342d) variant of the DES gene, in addition to semitendinosus and fibula, Cardiac involvement is relatively insidious and easy to be ignored in clinic. Timely muscle MRI, muscle biopsy and gene detection will help the early diagnosis of the disease.

Genetic analysis of a Chinese pedigree affected with Becker muscular dystrophy with myalgia as the main feature / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a Chinese pedigree affected with Becker muscular dystrophy (BMD) with myalgia as the main feature.@*METHODS@#Clinical data of the patients and results of auxiliary examinations were retrospectively analyzed. Multiplex ligation-dependent probe amplification and high-throughput sequencing were used to detect potential variants. Sanger sequencing was used to verify the results.@*RESULTS@#The clinical manifestations of the proband included myalgia and elevated serum creatine kinase, which is similar to another patient from the pedigree. Genetic testing revealed that the two patients both harbored hemizygous deletions of exons 10 to 29 of the DMD gene, for which the mother was a carrier. The same deletion was not found in his father. Based on the guidelines from American College of Medical Genetics and Genomics, the deletion was predicted to be pathogenic (PVS1+PM2+PP1).@*CONCLUSION@#Myalgia with elevated serum CK may be atypical clinical manifestations of BMD and may be associated with variants in the rod domain of the DMD gene. The deletion of exons 10 to 29 of the DMD gene probably underlay the BMD in this pedigree.