Genetic architecture of ALS in Sardinia.
Genetic architecture of ALS in Sardinia.
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DOI：
10.1016/j.neurobiolaging.2014.07.012
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发表时间：
2014-12
影响因子：
4.2
通讯作者：
ITALSGEN and SARDINALS Consortia
中科院分区：
文献类型：
--
作者：
Borghero G;Pugliatti M;Marrosu F;Marrosu MG;Murru MR;Floris G;Cannas A;Parish LD;Occhineri P;Cau TB;Loi D;Ticca A;Traccis S;Manera U;Canosa A;Moglia C;Calvo A;Barberis M;Brunetti M;Pliner HA;Renton AE;Nalls MA;Traynor BJ;Restagno G;Chiò A;ITALSGEN and SARDINALS Consortia
保守的人群，如撒丁岛人，显示家族性或散发性ALS的发病率升高，提供了关于该疾病遗传学的独特信息。我们的目的是描述一系列连续的撒丁岛血统的ALS患者的遗传特征。2008年至2013年期间通过ITALSGEN联盟确定的所有撒丁岛血统的ALS患者都有资格入选本研究。患者和对照组进行了TARDBP，C9ORF72，SOD1和FUS基因的分析。在375例撒丁岛ALS病例中的155例（41.3%）中鉴定出遗传突变，更常见的是TARDBP的p.A382T和p.G295S突变，以及C9ORF72的GGGGCC六核苷酸重复扩增。1例患者同时具有TARDBP的p.G295S和p.A382T突变，8例患者同时具有TARDBP的杂合p.A382T突变和C9ORF72的重复扩增。携带TARDBP的p.A382T和p.G295S突变以及C9ORF72重复扩增的患者在这些基因座上共享不同的单倍型。同时出现C9ORF72和TARDBP p.A382T错义突变的患者发病年龄明显较低，生存期较短。撒丁岛上超过40%的病例携带ALS相关基因的突变，这是斯堪的纳维亚半岛以外遗传学解释的ALS病例的最高百分比。与不同基因突变相关的临床表型显示出一些独特的特征，但携带相同突变的家庭之间的异质性意味着ALS的表现受到其他遗传和非遗传因素的影响。
Conserved populations, such as Sardinians, displaying elevated rates of familial or sporadic ALS provide unique information on the genetics of the disease. Our aim was to describe the genetic profile of a consecutive series of ALS patients of Sardinian ancestry. All ALS patients of Sardinian ancestry, identified between 2008 and 2013 through the ITALSGEN consortium, were eligible to be included in the study. Patients and controls underwent the analysis of TARDBP, C9ORF72, SOD1, and FUS genes. Genetic mutations were identified in 155 out of 375 Sardinian ALS cases (41.3%), more commonly the p.A382T and p.G295S mutations of TARDBP, and the GGGGCC hexanucleotide repeat expansion of C9ORF72. One patient had both p.G295S and p.A382T mutation of TARDBP and eight carried both the heterozygous p.A382T mutation of TARDBP and a repeat expansion of C9ORF72. Patients carrying the p.A382T and the p.G295S mutations of TARDBP and the C9ORF72 repeat expansion shared distinct haplotypes across these loci. Patients with co-occurrence of C9ORF72 and TARDBP p.A382T missense mutation had a significantly lower age at onset and shorter survival. More than 40% of all cases on the island of Sardinia carry a mutation of an ALS-related gene, representing the highest percentage of ALS cases genetically explained outside of Scandinavia. Clinical phenotypes associated with different genetic mutations show some distinctive characteristics, but the heterogeneity between and among families carrying the same mutations implies that ALS manifestation is influenced by other genetic and non-genetic factors.
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DOI：
10.1016/s1474-4422(12)70043-1
发表时间：
2012-04
期刊：
The Lancet. Neurology
影响因子：
--
作者：
Majounie E;Renton AE;Mok K;Dopper EG;Waite A;Rollinson S;Chiò A;Restagno G;Nicolaou N;Simon-Sanchez J;van Swieten JC;Abramzon Y;Johnson JO;Sendtner M;Pamphlett R;Orrell RW;Mead S;Sidle KC;Houlden H;Rohrer JD;Morrison KE;Pall H;Talbot K;Ansorge O;Chromosome 9-ALS/FTD Consortium;French research network on FTLD/FTLD/ALS;ITALSGEN Consortium;Hernandez DG;Arepalli S;Sabatelli M;Mora G;Corbo M;Giannini F;Calvo A;Englund E;Borghero G;Floris GL;Remes AM;Laaksovirta H;McCluskey L;Trojanowski JQ;Van Deerlin VM;Schellenberg GD;Nalls MA;Drory VE;Lu CS;Yeh TH;Ishiura H;Takahashi Y;Tsuji S;Le Ber I;Brice A;Drepper C;Williams N;Kirby J;Shaw P;Hardy J;Tienari PJ;Heutink P;Morris HR;Pickering-Brown S;Traynor BJ
通讯作者：
Traynor BJ
影响因子：
4
作者：
Kenna KP;McLaughlin RL;Byrne S;Elamin M;Heverin M;Kenny EM;Cormican P;Morris DW;Donaghy CG;Bradley DG;Hardiman O
通讯作者：
Hardiman O
影响因子：
25
作者：
Renton AE;Chiò A;Traynor BJ
通讯作者：
Traynor BJ
影响因子：
14.5
作者：
Chio, Adriano;Borghero, Giuseppe;Sabatelli, Mario
通讯作者：
Sabatelli, Mario
影响因子：
25
作者：
Johnson, Janel O.;Pioro, Erik P.;Boehringer, Ashley;Chia, Ruth;Feit, Howard;Renton, Alan E.;Pliner, Hannah A.;Abramzon, Yevgeniya;Marangi, Giuseppe;Winborn, Brett J.;Gibbs, J. Raphael;Nalls, Michael A.;Morgan, Sarah;Shoai, Maryam;Hardy, John;Pittman, Alan;Orrell, Richard W.;Malaspina, Andrea;Sidle, Katie C.;Fratta, Pietro;Harms, Matthew B.;Baloh, Robert H.;Pestronk, Alan;Weihl, Conrad C.;Rogaeva, Ekaterina;Zinman, Lorne;Drory, Vivian E.;Borghero, Giuseppe;Mora, Gabriele;Calvo, Andrea;Rothstein, Jeffrey D.;Drepper, Carsten;Sendtner, Michael;Singleton, Andrew B.;Taylor, J. Paul;Cookson, Mark R.;Restagno, Gabriella;Sabatelli, Mario;Bowser, Robert;Chio, Adriano;Traynor, Bryan J.
通讯作者：
Traynor, Bryan J.