講演情報
[S4-3]筋疾患における大規模ゲノム配列解析 − 現状と展望
○西野 一三 (国立精神・神経医療研究センター 神経研究所 疾病研究第一部)
Muscle pathology still plays an important role in the diagnosis of muscle diseases as many are defined at least partly by pathological findings. Our lab has been screening for mutations in patients myopathologically diagnosed or suspected to have muscle disease by using 4 sequencing panels covering known muscle-disease-causative genes. Recently, we have designed “HM panel” covering 115 known causative genes of hereditary muscle diseases whose mutations have been confirmed in at least two unrelated Japanese patients. Now we conduct a comprehensive mutation screening in basically all the patients whose muscle pathology diagnosis was made in our lab. When genetic diagnosis is unconfirmed, we further perform whole exome (WES) and/or whole genome sequencing (WGS). However, simple WES/WGS rarely leads to the final diagnosis, which may be because: 1) the disease is not a hereditary muscle disease, 2) the mutation is located in the region that is not analyzed, or 3) the mutation is caused by a repetitive sequence that cannot be detected by short-read sequencing. In fact, some cases that were diagnosed as muscular dystrophy in the past were later found to be myositis. Deep intron mutations in DMD gene were found by combining long-read sequencing with RNA-seq. Recently, oculopharyngodistal myopathy was shown to be caused by the elongation of CGG repeats in the 5' untranslated region of LRP12 gene. In my talk, I would like to discuss the current status and challenges in the genetic diagnosis of muscle diseases, as well as future developments, by presenting some examples.