Aberrant mRNA processing caused by splicing mutations in TTN-related neuromuscular disorders

Mutations in the TTN gene have been reported to be responsible for a range of neuromuscular disorders, including recessive distal myopathy and congenital myopathy (CM). Only five splicing mutations have been identified to induce aberrant mRNA splicing in TTN-related neuromuscular disorders. In our study, we described detailed clinical characteristics, muscle pathology and genetic analysis of two probands with TTN-related autosomal recessive neuromuscular disorders. Besides, we identified two novel intronic mutations, c.107377+1 G > C in intron 362 and c.19994-2 A > G in intron 68, in the two probands. Through cDNA analysis, we revealed the c.107377+1 G > C mutation induced retention of the entire intron 362, and the c.19994-2 A > G mutation triggered skipping of the first 11 bp of exon 69. Our study broadens the aberrant splicing spectrum of neuromuscular disorders caused by splicing mutations in the TTN gene.