講演情報
[O10-3]臨床的にSMAと診断される患者のSMN1遺伝子領域のゲノム解析研究
○加藤 環1, 横村 守1, 大澤 裕2, 松尾 憲典3, 久保 祐二1, 本間 泰平4, 齋藤 加代子1 (1.東京女子医科大学 ゲノム診療科, 2.川崎医科大学 神経内科, 3.京都田辺中央病院 小児科, 4.バイオジェン・ジャパン株式会社)
【Objective】Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene. Genomic analyses to identify patients with 5q-SMA by gene mutation identification and to clarify single nucleotide variants (SNVs) in SMN1 may help in determining a therapeutic target for SMA. However, SMN1 gene sequencing is difficult owing to the presence of the homologous SMN2 gene. We examined SNVs in the entire SMN1 region in patients with clinically diagnosed SMA using a new method combining long-range polymerase chain reaction (LR-PCR) with next-generation sequencing (NGS).【Methods】Multiplex Ligation-dependent Probe Amplification was performed on 323 patient DNA samples (January 2017 to March 2019); 158 samples with exon 8 deletions in SMN1 were excluded. Of the remaining 165 samples, 62 samples with informed consent and motor function data were eligible and analyzed by LR-PCR with NGS.【Results】NGS was completed on all 62 samples. Pathogenic mutations were identified in 2 patient samples; 1 patient, whose parents were cousins, had 2 copies of SMN1 and a homozygous variant. Overall, there were 7, 7, 45, and 3 patients who had 0, 1, 2, and 3 copies of exon 7 of SMN1, respectively. The number of SNVs identified in an intronic region was 17, 6, 3, 12, 2, and 23 in introns 1, 2a, 2b, 4, 5, and 6, respectively.【Conclusion】In this genomic analysis of 62 DNA samples from patients with clinically diagnosed SMA, SNVs were concentrated in intron 6, with 2 patients genetically diagnosed with 5q-SMA.