A.3 A novel recessive TNNT1 congenital core-rod myopathy in French Canadians

Background: Mutations in the slow skeletal muscle troponin T ( TNNT1 ) gene cause a congenital nemaline myopathy resulting death from respiratory insufficiency early infancy. We report on four French Canadians with novel myopathy. Methods: Patients underwent lower extremity and paraspinal MRI, quadriceps biopsy genetic testing. expression was assessed by quantitative PCR immunoblotting. Wild type or mutated mRNAs were co-injected morpholinos zebrafish knockdown model to assess for rescue of morphant phenotype. Results: Four patients shared missense homozygous mutation . They developed childhood slowly progressive limb-girdle weakness spinal rigidity contractures. suffered restrictive lung disease recurrent episodes rhabdomyolysis. Older remained ambulatory into their sixties. Lower MRI showed symmetrical myopathic changes. Paraspinal diffuse fibro-fatty involution. Biopsies multi-minicores. Nemaline rods seen half patients. mRNA similar controls patients, while levels protein reduced rescued morphants but mutant transcripts failed do so. Conclusions: This study expands spectrum -related include milder clinical phenotype caused functionally-confirmed mutation.