Tampere Neuromuscular Center, Tampere University Hospital, Tampere.
Folkhalsan Institute of Genetics, Department of Medical Genetics, University of Helsinki, Helsinki.
Curr Opin Neurol. 2020 Oct;33(5):604-610. doi: 10.1097/WCO.0000000000000850.
The last few years have confirmed previous assumptions of an enormous impact of the titin gene (TTN) on the occurrence of muscle disease, cardiomyopathy, or both together. The reason for this rather late understanding of its importance is because of the huge size which prevented sequencing of the whole gene by the previous Sanger technique in the individual cases. An update of the advances in diagnosing titinopathies is the main focus of this review.
High throughput methods are now widely available for TTN sequencing and a corresponding explosion of different types of identified titinopathies is observed and published in the literature, although final confirmation is lacking in many cases with recessive missense variants.
The implications of these findings for clinical practice are easy to understand: patients with previously undiagnosed muscle disease can now have a correct diagnosis and subsequently receive a likely prognosis, can have accurate genetic counseling for the whole family and early treatment for predictable complications from the heart and respiratory muscles. In addition not to forget, they can avoid wrong diagnoses leading to wrong treatments.
过去几年证实了肌病、心肌病或两者同时发生与肌联蛋白（TTN）基因的巨大影响之前的假设。之所以对其重要性的认识相对较晚，是因为其巨大的尺寸使得之前的桑格技术无法在个体病例中对整个基因进行测序。本综述的主要重点是对肌联蛋白病诊断进展的更新。
现在有高通量方法可用于 TTN 测序，并且在文献中观察到并发表了大量不同类型的已识别肌联蛋白病，尽管在许多情况下，隐性错义变体缺乏最终确认。
这些发现对临床实践的影响是显而易见的：现在患有以前未确诊的肌肉疾病的患者可以得到正确的诊断，随后可以得到可能的预后，可以对整个家族进行准确的遗传咨询，并对心脏和呼吸肌的可预测并发症进行早期治疗。此外，不要忘记，他们可以避免导致错误治疗的错误诊断。
