PT -期刊文章盟Daniela Piga AU -达里奥Ronchi盟弗朗西斯卡Magri AU -普螺旋器非盟- Serena Ghezzi盟Eugenio麦克利AU -恩里科·贝尔蒂尼AU -安东尼奥Toscano AU -伊莎贝拉莫罗尼盟Maurizio Moggio AU -玛丽亚德安杰洛盟克劳迪奥·布鲁诺AU -滨莫拉盟Nereo Bresolin AU - Giacomo Comi TI -下一代测序分析的一个意大利患者群受到Nemaline肌病(P07.035) DP - 2013年2月12日TA -神经病学PG - P07.035 P07.035 VI - 80 IP - 7补充4099 - //www.ez-admanager.com/content/80/7_Supplement/P07.035.short 4100 - //www.ez-admanager.com/content/80/7_Supplement/P07.035.full所以Neurology2013 2月12;首页80 AB -目的:我们使用新一代测序(上天)分析Nebulin(内)基因在一群意大利nemaline肌病患者(NM)。背景:纳米是一个临床和异构障碍引起的骨骼肌基因突变在五个不同的基因编码的薄丝蛋白的横纹肌肌小节。突变内负责大约50%的病例。70年内突变,主要是小的缺失或点突变,已经出版。内是最大的和更复杂的基因参与神经肌肉疾病,使其分析传统测序方法耗时又昂贵。考虑到固有的基因的复杂性,我们选择捷作为替代技术。设计/方法:我们分析了10个意大利患者NM,以前ACTA1筛查,TPM2, TPM3, TNNT1 CFL2。我们使用目标区域捕获测序深度调查内,寻找突变在所有183个外显子,内含子、启动子区域。桑格变更已确认。RESULTS: We have found 9 novel NEB variants: missense mutations, affecting conserved amino acids; small indels causing frame shifts; nonsense mutations responsible for premature truncation of nebulin; splice-site mutations. In addition, we have found a deletion in the middle of intron 125 causing the partial inclusion of intron in the coding sequence.CONCLUSIONS: We have found mutations in 7 out of 10 patients, the highest detection rate observed in a selected cohort of NM patients. The application of the Target Region Capture Sequencing allowed a faster determination of recessive missense mutations, compound heterozygote genotypes, small deletions, stop codon and frame shifts. The target analysis has allowed to improve the quality and depth of data. We conclude that this method appears promising for a quicker detection of mutations in complex genes like NEB, with large coding size, exon number and without obvious mutational hotspots.Disclosure: Dr. Piga has nothing to disclose. Dr. Ronchi has nothing to disclose. Dr. Magri has nothing to disclose. Dr. Corti has nothing to disclose. Dr. Ghezzi has nothing to disclose. Dr. Mercuri has received personal compensation for activities with Aceleron Pharma, PTC Therapeutics, Inc., and Genzyme Corporation. Dr. Mercuri has received personal compensation in an editorial capacity for Neuromuscular Disorders, Annals of Neurology, Developmental Medicine & Child Neurology, and Neuropediatric. Dr. Bertini has received research support from Telethon Italy and SMA Europe. Dr. Toscano has nothing to disclose. Dr. Moroni has nothing to disclose. Dr. Moggio has nothing to disclose. Dr. D'Angelo has nothing to disclose. Dr. Bruno has nothing to disclose. Dr. Mora has nothing to disclose. Dr. Bresolin has nothing to disclose. Dr. Comi has received research support from Telethon Italy and SMA Europe.Thursday, March 21 2013, 2:00 pm-7:00 pm