SHC2 gene copy number in multiple system atrophy (MSA).
SHC2 gene copy number in multiple system atrophy (MSA).
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DOI：
10.1007/s10286-013-0216-8
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发表时间：
2014-02
影响因子：
5.8
通讯作者：
Robertson, David
中科院分区：
文献类型：
--
作者：
Ferguson, Marcus C.;Garland, Emily M.;Hedges, Lora;Womack-Nunley, Bethany;Hamid, Rizwan;Phillips, John A., III;Shibao, Cyndya A.;Raj, Satish R.;Biaggioni, Italo;Robertson, David
多系统萎缩(MSA)是一种散发性、起病晚、进展迅速的神经退行性疾病，其特征是自主神经功能衰竭，并伴有帕金森病、小脑和锥体运动症状。病理特征是胶质细胞质内含α-突触核蛋白聚合体。因此，MSA是一种阿尔法突触核病。最近，Sasaki et al.报道在许多日本MSA患者的DNA中存在含有SHC2基因拷贝数丢失的杂合性(杂合性SHC2基因缺失)。由于背景拷贝数变异(CNV)在不同的人群中可能是不同的，我们评估了来自美国MSA患者队列的DNA中的SHC2等位基因拷贝数，以确定在美国MSA转诊中心跟踪的美国队列中SHC2基因拷贝数变异的贡献。我们的队列包括105名仔细分型的MSA患者。我们研究了105名特征良好的MSA患者和5名SHC2基因拷贝数减少的对照组。我们用两种TaqMan基因拷贝数测定方法，确定了SHC2基因的两个相隔27kb的片段的拷贝数。我们所有105名MSA患者的DNA检测结果显示，他们的SHC2基因的两个片段都有两个副本。我们的结果表明，SHC2基因缺失是美国人群中极少数(如果有的话)特征良好的MSA病例的基础。这与佐佐木等人报告的日本经验相反，可能反映了这种疾病在不同遗传背景下的异质性。
Multiple system atrophy (MSA) is a sporadic, late onset, rapidly-progressing neurodegenerative disorder, which is characterized by autonomic failure, together with parkinsonian, cerebellar, and pyramidal motor symptoms. The pathologic hallmark is the glial cytoplasmic inclusion with alpha-synuclein aggregates. MSA is thus an alpha synucleinopathy. Recently, Sasaki et al. reported that heterozygosity for copy number loss of Src homology 2 domain containing-transforming protein 2 (SHC2) genes (heterozygous SHC2 gene deletions) occurred in DNAs from many Japanese individuals with MSA. Because background copy number variation (CNV) can be distinct in different human populations, we assessed SHC2 allele copy number in DNAs from a US cohort of individuals with MSA, to determine the contribution of SHC2 gene copy number variation in an American cohort followed at a US referral center for MSA. Our cohort included 105 carefully phenotyped individuals with MSA. We studied 105 well characterized patients with MSA and 5 control subjects with reduced SHC2 gene copy number. We used two TaqMan Gene Copy Number Assays, to determine the copy number of two segments of the SHC2 gene that are separated by 27 Kb. Assay results of DNAs from all of our 105 subjects with MSA showed two copies of both segments of their SHC2 genes. Our results indicate that SHC2 gene deletions underlie few, if any, cases of well characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds.
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影响因子：
11.2
作者：
Scholz, Sonja W.;Houlden, Henry;Schulte, Claudia;Sharma, Manu;Li, Abi;Berg, Daniela;Melchers, Anna;Paudel, Reema;Gibbs, J. Raphael;Simon-Sanchez, Javier;Paisan-Ruiz, Coro;Bras, Jose;Ding, Jinhui;Chen, Honglei;Traynor, Bryan J.;Arepalli, Sampath;Zonozi, Ryan R.;Revesz, Tamas;Holton, Janice;Wood, Nick;Lees, Andrew;Oertel, Wolfgang;Wuellner, Ullrich;Goldwurm, Stefano;Pellecchia, Maria Teresa;Illig, Thomas;Riess, Olaf;Fernandez, Hubert H.;Rodriguez, Ramon L.;Okun, Michael S.;Poewe, Werner;Wenning, Gregor K.;Hardy, John A.;Singleton, Andrew B.;Gasser, Thomas
通讯作者：
Gasser, Thomas
影响因子：
11
作者：
通讯作者：
--
影响因子：
8.6
作者：
Soma, Hiroyuki;Yabe, Ichiro;Sasaki, Hidenao
通讯作者：
Sasaki, Hidenao
影响因子：
4.4
作者：
PAPP, MI;KAHN, JE;LANTOS, PL
通讯作者：
LANTOS, PL
影响因子：
3.6
作者：
Sasaki H;Emi M;Iijima H;Ito N;Sato H;Yabe I;Kato T;Utsumi J;Matsubara K
通讯作者：
Matsubara K