G.P.16 Myopathy with lobulated fibers, cores and rods caused by a COL6 mutation

Abstract

We report on a 49-year-old female patient who developed since childhood a slowly progressive proximal muscle weakness, more pronounced in the lower limbs. She sometimes complains about myalgias. She presents a waddling gait, Gowers‘ sign, axial weakness (neck flexors and abdominal muscles), contractures of the finger flexors and elbows. She showed no signs of facial weakness, scapular winging, hyperlaxity, scoliosis or skin lesions. Her medical antecedents revealed a myocarditis and a miscarriage. She has two affected daughters and one unaffected son. Her mother and maternal grandmother also had proximal muscle weakness. Serum CK was slightly elevated (215U/l; normal <140). Electromyography showed mild myopathic changes. Both cardiac exams (24h-holter-ECG, echocardiography) and respiratory exams were normal. The muscle biopsy (lateral vastus muscle; 49years) revealed a large number of small lobulated fibers, as well as fibers with cores and rods. Furthermore, the biopsy showed an increased variability in muscle fiber size, an increased number of internalized nuclei and a type 1 fiber predominance. The small lobulated fibers were of type 1, whereas the larger fibers were of type 2. The immunohistochemical stainings for a large number of proteins, including collagen-VI, were normal. The immunoblot analyses were also normal. The ultrastructural analyses confirmed the presence of lobulated fibers, cores and nemaline bodies. Because of this “core-rod“ myopathy, mutations in RYR1 and ACTA1 were excluded. We then performed a whole-body muscle MRI (1.5Tesla), which showed peripheral involvement and central sparing of the leg muscles, compatible with a collagenopathy (Bethlem myopathy). Indeed, sequencing of the COL6A3-gene revealed a heterozygous mutation in exon 17 (c.6239G>A; p.Gly2080Asp). We conclude that in patients with a myopathy with cores, rods and lobulated fibers, mutations in COL6 should be considered.