講演情報
[O13-1]CANVASはrepeat conformation heterogeneityを有する
○宮武 聡子1,2, 吉田 邦広3, 輿水 江里子2, 土井 宏4, 福田 裕美2,4, 濱中 耕平2, 田中 章景4, 水口 剛2, 松本 直通2 (1.横浜市立大学附属病院 遺伝子診療科, 2.横浜市立大学医学研究科遺伝学教室, 3.信州大学医学部神経難病学講座 神経遺伝学部門, 4.横浜市立大学 脳神経内科学・脳卒中医学)
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive multisystem neurodegenerative disorder. To molecularly characterize this disease in patients with adult-onset ataxia, we analyzed 212 of such Japanese families by an integrated approach including flanking PCR, repeat-primed PCR, Southern blotting, and long-read sequencing (LRS) using three different sequencers. LRS successfully identified entire repeat expansion at the nucleotide level of resolution. We identified 16 patients from 11 families; 7 had ACAGG homozygous repeat expansion, 2 had ACAGG and AAGGG compound repeat expansions, and 7 had AAGGG homozygous repeat expansions. Thus, the diagnostic rate was 5.2 %. Clinical assessment of these patients implied that patients with ACAGG expansions share similar clinical features with patients with AAGGG expansions, although motor neuron involvement was more apparent in patients with ACAGG expansions. To validate the sequence accuracy of the three different sequencers, we compared the expanded repeat length obtained from Southern blotting with one from any of three sequencers and found the significant correlations between them. We report the repeat conformation heterogeneity in CANVAS, and possibility of different impacts on the affected nervous systems depending on the repeat configuration. Long-read sequencing is a powerful method for analyzing repeat expansion diseases.