Two siblings of French-Canadian descent, a 52-year-old male and a 61-year-old female, have developed since childhood a slowly progressive proximal muscle weakness and severe joint contractures. They were of short stature, and had small muscle bulk, kyphoscoliosis, rigid spine, Gowers sign and hypoactive reflexes. They walked unaided, although the gait was slow owing to hip contractures. None of the patients’ seven siblings or parents had similar features. Muscle biopsies showed similar findings of sarcoplasmic or cap rods, central cores or minicores and lobulated fibers caused by subsarcolemmal accumulation of small abnormal mitochondria. Fiber type disproportion and selective type I fiber atrophy were lacking. Next-generation sequencing gene panel identified a shared novel missense homozygous mutation in the TNNT1 gene (c.287T>C; p.L96P). The mutation in TNNT1 exon 7 is predicted pathogenic by damaging the tropomyosin-binding site 1 structure of the slow skeletal muscle troponin T (ssTnT), thereby reducing its affinity for tropomyosin. The unusual muscle pathological findings of rods, cores/minicores and lobulated fibers have not been previously described in nemaline myopathy.

These cases expand the clinical, genetic and histopathological spectrums of autosomal recessive NEM5. Our findings support that TNNT1 gene mutations should be considered as a cause of milder congenital myopathies.