Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
Laboratoire de Génétique Moléculaire de Maladies Rares, EA 7402, Université de Montpellier, Montpellier, France.
Ann Clin Transl Neurol. 2020 May;7(5):846-854. doi: 10.1002/acn3.51031. Epub 2020 Apr 19.
Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss. Immunohistochemistry and Western blotting revealed a marked reduction of fast myosin heavy chain isoforms. This is the first observation of a titinopathy suggesting that titin defect leads to secondary loss of fast myosin heavy chain isoforms.
先天性 titin 病是一种具有多种表型和遗传方式的肌病。在这里，我们采用综合方法（深度表型分析、肌肉形态学、肌肉活检中的 mRNA 和蛋白质评估）全面描述了两名患有先天性多核肌病的兄弟姐妹，他们携带三个预测会影响 titin 稳定性和 titin-myosin 相互作用的 TTN 变异体。肌肉活检显示多核、1 型纤维均匀性和肌节结构破坏，伴有一些粗丝丢失。免疫组化和 Western blot 显示快速肌球蛋白重链同工型明显减少。这是 titin 病的首次观察结果，表明 titin 缺陷导致快速肌球蛋白重链同工型的继发性丢失。
