遗传流行病学的C9ORF72 ALS:一个国家研究在意大利(P7.005)

文摘

背景。GGGGCC hexanucleotide重复扩张C9ORF72第一内含子的基因代表白人血统的ALS患者最常见的突变。欧洲C9ORF72突变的频率有南北梯度下降。的目标。评估频率和临床特点C9ORF72突变意大利大陆和狭隘。方法。所有16个意大利ALS ALS患者中心检测C9ORF72, SOD1,付家,TARDBP突变。病人的地理起源已经决定通过一个详细的评估他们的谱系。结果。共有3868名ALS患者中,268 (6.9%)C9ORF72突变,其中50%有阳性家族史对肌萎缩性侧索硬化症或额颞叶痴呆。 The mean age at onset of patients with C9ORF72 mutation was 58.3 (SD 9.4) years, lower than that of cases not carrying the mutation (61.1, SD 12.7) (p=0.0001). No difference in the mean age at onset was found in C9ORF72 patients with positive or negative family history or with bulbar or spinal onset. The frequency of mutations was similar in continental Italy as well in Sicily, while it was significantly higher in Sardinia (12.8% of cases). However, a cluster of C9ORF72 mutations (12.7% of all cases) has been found also in Basilicata, a relatively isolated region of southern Italy, completely surrounded by the Apennines and with only small tracts of coastline. No clinical differences (age and site of onset, cognitive impairment, survival) were found between patients with different regional ancestry. These patients carry a common risk haplotype confirming a founder effect. Conclusions. The frequency of C9ORF72 mutations in Italy is lower than that reported in northern Europe. We fund no clear north-to-south pattern of frequency of C9ORF72 frequency in Italy, with the remarkable exception of two geographical isolates, Sardinia and Basilicata. Regional ancestry do not influence the phenotype of C9ORF72 ALS. Study Supported by: Health Seventh Framework Programme (No 259867); Italian Ministry of Health (RF-2010-2309849)

披露:Battistini博士没有披露。卡尔沃博士没有披露。Caponnetto博士没有披露。Conforti博士没有披露。Corbo博士没有披露。Giannini博士没有披露。Mandrioli博士没有披露。Salvi博士接到这个基金会Hilarescere研究支持。莫拉博士没有披露。Sabatelli博士没有披露。 Dr. La Bella has nothing to disclose. Dr. Logroscino has received personal compensation for activities with Novartis, GlaxoSmithKline Inc., and Boerhinger Ingelheim Pharmaceuticals, Inc. Dr. Simone has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., and Biogen Idec. Dr. Monsurrò has nothing to disclose. Dr. Mazzini has nothing to disclose. Dr. Borghero has nothing to disclose. Dr. Logullo has nothing to disclose. Dr. Lunetta has nothing to disclose. Dr. Volanti has nothing to disclose. Dr. Pugliatti has nothing to disclose. Dr. Mandich has nothing to disclose. Dr. D'Alfonso has nothing to disclose. Dr. Penco has nothing to disclose. Dr. Zollino has nothing to disclose. Dr. Murru has nothing to disclose. Dr. Restagno has nothing to disclose.