Limb-girdle muscular dystrophy R7 telethonin-related (LGMDR7) is a rare autosomal recessive disorder caused by TCAP gene mutations. This study described the phenotypic spectrum, genetic characteristics, and muscle magnetic resonance imaging (MRI) findings of patients with LGMDR7. Five patients from three unrelated families with TCAP mutations were retrospectively identified at the Neuromuscular Center at King Chulalongkorn Memorial Hospital. Demographic, clinical, laboratory, and muscle MRI data were collected and analyzed. We observed a mild phenotype associated with asymptomatic/paucisymptomatic hyperCKemia in one family and a classic limb-girdle muscular dystrophy phenotype in two unrelated patients. The novel deletion variant c.136_137del was identified in a compound heterozygous state with c.26_33dup in a family with a mild phenotype. Muscle MRI of four patients revealed consistent sparing of the sartorius muscle in all patients. This study expands the clinical and genetic spectrum of LGMDR7 by demonstrating an asymptomatic/paucisymptomatic hyperCKemia phenotype and identifying the novel c.136_137del variant. The muscle MRI findings highlight a characteristic pattern in which the sartorius muscle is consistently uninvolved. These findings contribute to a better understanding of the disease and assist in developing future diagnostic strategies for affected individuals, specifically by using clinical profiles in conjunction with the characteristics of muscle MRI.

Limb-girdle muscular dystrophy (LGMD) is a group of clinically and genetically heterogeneous neuromuscular disorders. LGMD-R7, which is caused by telethonin gene (TCAP) mutations, is one of the rarest forms of LGMD, and only a small number of LGMD-R7 cases have been described and mostly include patients from Brazil. A total of two LGMD-R7 patients were enrolled at a Chinese neuromuscular center. Demographic and clinical data were collected. Laboratory investigations and electromyography were performed. Routine and immunohistochemistry staining of muscle specimens was performed, and a next-generation sequencing panel array for genes associated with hereditary neuromuscular disorders was used for analysis. The patients exhibited predominant muscle weakness. Electromyography revealed myopathic changes. The muscle biopsy showed myopathic features, such as increased fiber size variation, muscle fiber atrophy and regeneration, slight hyperplasia of the connective tissue, and disarray of the myofibrillar network. Two patients were confirmed to have mutations in the open reading frame of TCAP by next-generation sequencing. One patient had compound heterozygous mutations, and the other patient harbored a novel homozygous mutation. Western blotting analysis of the skeletal muscle lysate confirmed the absence of telethonin in the patients. We described two LGMD-R7 patients presenting a classical LGMD phenotype and a novel homozygous TCAP mutation. Our research expands the spectrum of LGMD-R7 due to TCAP mutations based on patients from a Chinese neuromuscular center.

Limb girdle muscular dystrophy LGMD R7 telethonin-related is a rare autosomal recessive muscle disorder characterized by proximal muscle weakness of pelvic and shoulder girdles. Mutation in TCAP is responsible for LGMD R7, and the disease has a wide geographic distribution in diverse populations, but genotype-phenotype relationships remain unclear. We collected 5 LGMD R7 patients from three unrelated Chinese families. The average onset age was 16 ± 1.41; the initial symptoms included progressive proximal muscle weakness in limbs, difficulty in fast running, and asymmetric muscle atrophy in calves. Muscle MR imaging showed varying severity of fatty infiltration in the pelvic girdle, thigh, and calf muscles, and the severity of muscle infiltration was related to the length of the disease course. Muscle histopathology revealed aberrantly sized muscle fibers, internal nuclei, split fibers, rimmed vacuoles, monocyte invasion, and necrotic fibers. Sequencing identified one novel and one previously reported TCAP mutation. Our study extends the known distribution of this rare muscular dystrophy and presents the first detailed clinical and genetic characterizations of LGMD R7 cases from the Chinese population. Our work expands the mutation spectrum known for LGMD R7 and emphasizes the need for clinicians to consider TCAP mutations when evaluating patients with symptoms of limb girdle muscular dystrophy.