Wang Guangyu, Wu Wenjing, Lv Xiaoqing, Yan Chuanzhu, Lin Pengfei
Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
J Hum Genet. 2023 Nov;68(11):777-782. doi: 10.1038/s10038-023-01182-w. Epub 2023 Jul 5.
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.
据报道，TTN基因的突变与一系列神经肌肉疾病有关，包括隐性远端肌病和先天性肌病（CM）。在与TTN相关的神经肌肉疾病中，仅发现了5种剪接突变可诱导异常mRNA剪接。在我们的研究中，我们描述了两名患有与TTN相关的常染色体隐性神经肌肉疾病先证者的详细临床特征、肌肉病理学和基因分析。此外，我们在两名先证者中鉴定出两个新的内含子突变，分别为内含子362中的c.107377+1 G > C和内含子68中的c.19994-2 A > G。通过cDNA分析，我们发现c.107377+1 G > C突变导致整个内含子362保留，而c.19994-2 A > G突变引发外显子69的前11个碱基对缺失。我们的研究拓宽了由TTN基因剪接突变引起的神经肌肉疾病的异常剪接谱。
