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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.

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This study was funded by National Natural Science Foundation of China (Grant No. 82271436), Shandong Provincial Natural Science Foundation (Grant No. ZR2022MH190) and Qingdao Science and Technology Benefit People Demonstration Guide Special Project (Grant/Award Number: 22-8-7-smjk-1-nsh).

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Correspondence to Pengfei Lin.

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The authors declare no competing interests.

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This study was in compliance with the Declaration of Helsinki and approved by the Ethics Committee of Qilu Hospital of Shandong University. Informed consent was provided by the patient and parents.

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Wang, G., Wu, W., Lv, X. et al. Aberrant mRNA processing caused by splicing mutations in TTN-related neuromuscular disorders. J Hum Genet 68, 777–782 (2023).

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