A family with spinocerebellar ataxia type 5 found to have a novel missense mutation within a SPTBN2 spectrin repeat.
A family with spinocerebellar ataxia type 5 found to have a novel missense mutation within a SPTBN2 spectrin repeat.
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DOI：
10.1007/s12311-012-0408-0
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发表时间：
2013-04
期刊：
影响因子：
3.5
通讯作者：
Fogel, Brent L.
中科院分区：
文献类型：
--
作者：
Cho, Ellen;Fogel, Brent L.
一个临床诊断为脊髓小脑性共济失调5型（SCA 5）的家族中SPTBN 2基因新错义突变的鉴定一个迟发性常染色体显性纯小脑共济失调家族，与SCA 5一致，但缺乏以前报道的SPTBN 2突变，被确定。从两代的7个个体中收集DNA，并对11号染色体上的SPTBN 2基因进行测序。一个非同义杂合替换外显子12中检测到的个人诊断为SCA 5，而未受影响的家庭成员没有拥有这种变异。鉴定的c.1415C>T变体导致β-III血影蛋白的第二个SPEC结构域中的p.T472M置换。位置472处的苏氨酸不与限定SPEC结构域的特征性残基紧密接近，并且在不同的SPEC结构域中是可变的，但在SPTBN 2中是高度保守的。与这些观察结果一致，p.T472M变体的生物信息学分析表明它是病理性的。此前曾报道SPTBN 2 SPEC结构域内的两个缺失（E532_M544del和L629_R634delinsW）会导致SCA 5，但这是该蛋白质该区域中第一个被证明可能具有致病性的错义突变。
Identification of a novel missense mutation in the SPTBN2 gene of a family with a clinical diagnosis of spinocerebellar ataxia type 5 (SCA5). A family with late-onset autosomal dominant pure cerebellar ataxia, consistent with SCA5 but lacking previously reported SPTBN2 mutations, was identified. DNA was collected from seven individuals across two generations and the SPTBN2 gene on chromosome 11 was sequenced. A nonsynonymous heterozygous substitution in exon 12 was detected in individuals diagnosed with SCA5 while unaffected family members did not possess this variant. The identified c.1415C>T variant results in a p.T472M substitution in the second SPEC domain of the beta-III spectrin protein. The threonine at position 472 is not in close proximity to the characteristic residues that define the SPEC domain and is variable across diverse SPEC domains, yet is highly conserved in SPTBN2. Consistent with these observations, bioinformatic analysis of the p.T472M variant suggests it to be pathological. Two deletions within the SPTBN2 SPEC domains (E532_M544del and L629_R634delinsW) have been previously reported to cause SCA5, but this is the first missense mutation in this region of the protein shown to likely be pathogenic.
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影响因子：
7
作者：
Ng, PC;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
2.9
作者：
Ferrer-Costa, C;Orozco, M;de la Cruz, X
通讯作者：
de la Cruz, X
DOI：
10.1038/ncpneuro0319
发表时间：
2006-11-01
期刊：
NATURE CLINICAL PRACTICE NEUROLOGY
影响因子：
--
作者：
Fogel, Brent L.;Perlman, Susan
通讯作者：
Perlman, Susan
影响因子：
64.8
作者：
Altshuler, David;Durbin, Richard M.;Abecasis, Goncalo R.;Bentley, David R.;Chakravarti, Aravinda;Clark, Andrew G.;Collins, Francis S.;De la Vega, Francisco M.;Donnelly, Peter;Egholm, Michael;Flicek, Paul;Gabriel, Stacey B.;Gibbs, Richard A.;Knoppers, Bartha M.;Lander, Eric S.;Lehrach, Hans;Mardis, Elaine R.;McVean, Gil A.;Nickerson, DebbieA.;Peltonen, Leena;Schafer, Alan J.;Sherry, Stephen T.;Wang, Jun;Wilson, Richard K.;Gibbs, Richard A.;Deiros, David;Metzker, Mike;Muzny, Donna;Reid, Jeff;Wheeler, David;Wang, Jun;Li, Jingxiang;Jian, Min;Li, Guoqing;Li, Ruiqiang;Liang, Huiqing;Tian, Geng;Wang, Bo;Wang, Jian;Wang, Wei;Yang, Huanming;Zhang, Xiuqing;Zheng, Huisong;Lander, Eric S.;Altshuler, David L.;Ambrogio, Lauren;Bloom, Toby;Cibulskis, Kristian;Fennell, Tim J.;Gabriel, Stacey B.;Jaffe, David B.;Shefler, Erica;Sougnez, Carrie L.;Bentley, David R.;Gormley, Niall;Humphray, Sean;Kingsbury, Zoya;Koko-Gonzales, Paula;Stone, Jennifer;McKernan, Kevin J.;Costa, Gina L.;Ichikawa, Jeffry K.;Lee, Clarence C.;Sudbrak, Ralf;Lehrach, Hans;Borodina, Tatiana A.;Dahl, Andreas;Davydov, Alexey N.;Marquardt, Peter;Mertes, Florian;Nietfeld, Wilfiried;Rosenstiel, Philip;Schreiber, Stefan;Soldatov, Aleksey V.;Timmermann, Bernd;Tolzmann, Marius;Egholm, Michael;Affourtit, Jason;Ashworth, Dana;Attiya, Said;Bachorski, Melissa;Buglione, Eli;Burke, Adam;Caprio, Amanda;Celone, Christopher;Clark, Shauna;Conners, David;Desany, Brian;Gu, Lisa;Guccione, Lorri;Kao, Kalvin;Kebbel, Andrew;Knowlton, Jennifer;Labrecque, Matthew;McDade, Louise;Mealmaker, Craig;Minderman, Melissa;Nawrocki, Anne;Niazi, Faheem;Pareja, Kristen;Ramenani, Ravi;Riches, David;Song, Wanmin;Turcotte, Cynthia;Wang, Shally;Mardis, Elaine R.;Dooling, David;Fulton, Lucinda;Fulton, Robert;Weinstock, George;Durbin, Richard M.;Burton, John;Carter, David M.;Churcher, Carol;Coffey, Alison;Cox, Anthony;Palotie, Aarno;Quail, Michael;Skelly, Tom;Stalker, James;Swerdlow, Harold P.;Turner, Daniel;De Witte, Anniek;Giles, Shane;Gibbs, Richard A.;Wheeler, David;Bainbridge, Matthew;Challis, Danny;Sabo, Aniko;Yu, Fuli;Yu, Jin;Wang, Jun;Fang, Xiaodong;Guo, Xiaosen;Li, Ruiqiang;Li, Yingrui;Luo, Ruibang;Tai, Shuaishuai;Wu, Honglong;Zheng, Hancheng;Zheng, Xiaole;Zhou, Yan;Yang, Huanming;Marth, Gabor T.;Garrison, Erik P.;Huang, Weichun;Indap, Amit;Kural, Deniz;Lee, Wan-Ping;Leong, Wen Fung;Huang, Weichun;Indap, Amit;Kural, Deniz;Lee, Wan-Ping;Leong, Wen Fung;Quinlan, Aaron R.;Stewart, Chip;Stromberg, Michael P.;Ward, Alistair N.;Wu, Jiantao;Lee, Charles;Mills, Ryan E.;Shi, Xinghua;Daly, Mark J.;DePristo, Mark A.;Altshuler, David L.;Ball, Aaron D.;Banks, Eric;Bloom, Toby;Browning, Brian L.;Cibulskis, Kristian;Fennell, Tim J.;Garimella, Kiran V.;Grossman, Sharon R.;Handsaker, Robert E.;Hanna, Matt;Hartl, Chris;Jaffe, David B.;Kernytsky, Andrew M.;Korn, Joshua M.;Li, Heng;Maguire, Jared R.;McCarroll, Steven A.;McKenna, Aaron;Nemesh, James C.;Philippakis, Anthony A.;Poplin, Ryan E.;Price, Alkes;Rivas, Manuel A.;Sabeti, Pardis C.;Schaffner, Stephen F.;Shefler, Erica;Shlyakhter, Ilya A.;Cooper, David N.;Ball, Edward V.;Mort, Matthew;Phillips, Andrew D.;Stenson, Peter D.;Sebat, Jonathan;Makarov, Vladimir;Ye, Kenny;Yoon, Seungtai C.;Bustamante, Carlos D.;Clark, Andrew G.;Boyko, Adam;Degenhardt, Jeremiah;Gravel, Simon;Gutenkunst, Ryan N.;Kaganovich, Mark;Keinan, Alon;Lacroute, Phil;Ma, Xia;Reynolds, Andy;Clarke, Laura;Flicek, Paul;Cunningham, Fiona;Herrero, Javier;Keenen, Stephen;Kulesha, Eugene;Leinonen, Rasko;McLaren, WilliamM.;Radhakrishnan, Rajesh;Smith, Richard E.;Zalunin, Vadim;Zheng-Bradley, Xiangqun;Korbel, Jan O.;Stuetz, Adrian M.;Humphray, Sean;Bauer, Markus;Cheetham, R. Keira;Cox, Tony;Eberle, Michael;James, Terena;Kahn, Scott;Murray, Lisa;Ye, Kai;De La Vega, Francisco M.;Fu, Yutao;Hyland, Fiona C. L.;Manning, Jonathan M.;McLaughlin, Stephen F.;Peckham, Heather E.;Sakarya, Onur;Sun, Yongming A.;Tsung, Eric F.;Batzer, Mark A.;Konkel, Miriam K.;Walker, Jerilyn A.;Sudbrak, Ralf;Albrecht, Marcus W.;Amstislavskiy, Vyacheslav S.;Herwig, Ralf;Parkhomchuk, Dimitri V.;Sherry, Stephen T.;Agarwala, Richa;Khouri, Hodam.;Morgulis, Aleksandr O.;Paschall, Justin E.;Phan, Lon D.;Rotmistrovsky, Kirill E.;Sanders, Robert D.;Shumway, Martin F.;Xiao, Chunlin;McVean, Gil A.;Auton, Adam;Iqbal, Zamin;Lunter, Gerton;Marchini, Jonathan L.;Moutsianas, Loukas;Myers, Simon;Tumian, Afidalina;Desany, Brian;Knight, James;Winer, Roger;Craig, David W.;Beckstrom-Sternberg, Steve M.;Christoforides, Alexis;Kurdoglu, Ahmet A.;Pearson, Johnv.;Sinari, Shripad A.;Tembe, Waibhav D.;Haussler, David;Hinrichs, Angie S.;Katzman, Sol J.;Kern, Andrew;Kuhn, Robert M.;Przeworski, Molly;Hernandez, Ryan D.;Howie, Bryan;Kelley, Joanna L.;Melton, S. Cord;Abecasis, Goncalo R.;Li, Yun;Anderson, Paul;Blackwell, Tom;Chen, Wei;Cookson, William O.;Ding, Jun;Kang, Hyun Min;Lathrop, Mark;Liang, Liming;Moffatt, Miriam F.;Scheet, Paul;Sidore, Carlo;Snyder, Matthew;Zhan, Xiaowei;Zoellner, Sebastian;Awadalla, Philip;Casals, Ferran;Idaghdour, Youssef;Keebler, John;Stone, Eric A.;Zilversmit, Martine;Jorde, Lynn;Xing, Jinchuan;Eichler, Evan E.;Aksay, Gozde;Alkan, Can;Hajirasouliha, Iman;Hormozdiari, Fereydoun;Kidd, Jeffrey M.;Sahinalp, S. Cenk;Sudmant, Peter H.;Mardis, Elaine R.;Chen, Ken;Chinwalla, Asif;Ding, Li;Koboldt, Daniel C.;McLellan, Mike D.;Dooling, David;Weinstock, George;Wallis, John W.;Wendl, Michael C.;Zhang, Qunyuan;Durbin, Richard M.;Albers, Cornelis A.;Ayub, Qasim;Balasubramaniam, Senduran;Barrett, Jeffrey C.;Carter, David M.;Chen, Yuan;Conrad, Donald F.;Danecek, Petr;Dermitzakis, Emmanouil T.;Hu, Min;Huang, Ni;Hurles, Matt E.;Jin, Hanjun;Jostins, Luke;Keane, Thomas M.;Keane, Thomas M.;Le, Si Quang;Lindsay, Sarah;Long, Quan;MacArthur, Daniel G.;Montgomery, Stephen B.;Parts, Leopold;Stalker, James;Tyler-Smith, Chris;Walter, Klaudia;Zhang, Yujun;Gerstein, Mark B.;Snyder, Michael;Abyzov, Alexej;Abyzov, Alexej;Balasubramanian, Suganthi;Bjornson, Robert;Du, Jiang;Grubert, Fabian;Habegger, Lukas;Haraksingh, Rajini;Jee, Justin;Khurana, Ekta;Lam, Hugo Y. K.;Leng, Jing;Mu, Xinmeng Jasmine;Urban, Alexander E.;Zhang, Zhengdong;Li, Yingrui;Luo, Ruibang;Marth, Gabor T.;Garrison, Erik P.;Kural, Deniz;Quinlan, Aaron R.;Stewart, Chip;Stromberg, Michael P.;Ward, Alistair N.;Wu, Jiantao;Lee, Charles;Mills, Ryan E.;Shi, Xinghua;McCarroll, Steven A.;Banks, Eric;DePristo, Mark A.;Handsaker, Robert E.;Hartl, Chris;Korn, Joshua M.;Li, Heng;Nemesh, James C.;Sebat, Jonathan;Makarov, Vladimir;Ye, Kenny;Yoon, Seungtai C.;Degenhardt, Jeremiah;Kaganovich, Mark;Clarke, Laura;Smith, Richard E.;Zheng-Bradley, Xiangqun;Korbel, Jan O.;Humphray, Sean;Cheetham, R. Keira;Eberle, Michael;Kahn, Scott;Murray, Lisa;Ye, Kai;De la Vega, Francisco M.;Fu, Yutao;Peckham, Heather E.;Sun, Yongming A.;Batzer, Mark A.;Konkel, Miriam K.;Xiao, Chunlin;Iqbal, Zamin;Desany, Brian;Blackwell, Tom;Snyder, Matthew;Xing, Jinchuan;Eichler, Evan E.;Aksay, Gozde;Alkan, Can;Hajirasouliha, Iman;Hormozdiari, Fereydoun;Kidd, Jeffrey M.;Chen, Ken;Chinwalla, Asif;Ding, Li;McLellan, Mike D.;Wallis, John W.;Hurles, Matt E.;Conrad, Donald F.;Walter, Klaudia;Zhang, Yujun;Gerstein, Mark B.;Snyder, Michael;Abyzov, Alexej;Du, Jiang;Grubert, Fabian;Haraksingh, Rajini;Jee, Justin;Khurana, Ekta;Lam, Hugo Y. K.;Leng, Jing;Mu, Xinmeng Jasmine;Urban, Alexander E.;Zhang, Zhengdong;Gibbs, Richard A.;Bainbridge, Matthew;Challis, Danny;Coafra, Cristian;Dinh, Huyen;Kovar, Christie;Lee, Sandy;Muzny, Donna;Nazareth, Lynne;Reid, Jeff;Sabo, Aniko;Yu, Fuli;Yu, Jin;Marth, Gabor T.;Garrison, Erik P.;Indap, Amit;Leong, Wen Fung;Quinlan, Aaron R.;Stewart, Chip;Ward, Alistair N.;Wu, Jiantao;Cibulskis, Kristian;Fennell, Tim J.;Gabriel, Stacey B.;Garimella, Kiran V.;Hartl, Chris;Shefler, Erica;Sougnez, Carrie L.;Wilkinson, Jane;Clark, Andrew G.;Gravel, Simon;Grubert, Fabian;Clarke, Laura;Flicek, Paul;Smith, Richard E.;Zheng-Bradley, Xiangqun;Sherry, Stephen T.;Khouri, Hoda M.;Paschall, Justin E.;Shumway, Martin F.;Xiao, Chunlin;McVean, Gil A.;Katzman, Sol J.;Abecasis, Goncalo R.;Blackwell, Tom;Mardis, Elaine R.;Dooling, David;Fulton, Lucinda;Fulton, Robert;Koboldt, Daniel C.;Durbin, Richard M.;Balasubramaniam, Senduran;Coffey, Allison;Keane, Thomas M.;MacArthur, Daniel G.;Palotie, Aarno;Scott, Carol;Stalker, James;Tyler-Smith, Chris;Gerstein, Mark B.;Balasubramanian, Suganthi;Chakravarti, Aravinda;Knoppers, Bartha M.;Peltonen, Leena;Abecasis, Goncalo R.;Bustamante, Carlos D.;Gharani, Neda;Gibbs, Richard A.;Jorde, Lynn;Kaye, Jane S.;Kent, Alastair;Li, Taosha;McGuire, Amy L.;McVean, Gil A.;Ossorio, Pilar N.;Rotimi, Charles N.;Su, Yeyang;Toji, Lorraine H.;Tyler-Smith, Chris;Brooks, Lisa D.;Felsenfeld, Adam L.;McEwen, Jean E.;Abdallah, Assya;Juenger, Christopher R.;Clemm, Nicholas C.;Collins, Francis S.;Duncanson, Audrey;Green, Eric D.;Guyer, Mark S.;Peterson, Jane L.;Schafer, Alan J.;Abecasis, Goncalo R.;Altshuler, David L.;Auton, Adam;Brooks, Lisa D.;Durbin, Richard M.;Gibbs, Richard A.;Hurles, Matt E.;McVean, Gil A.
通讯作者：
McVean, Gil A.
影响因子：
14.9
作者：
Sherry, ST;Ward, MH;Sirotkin, K
通讯作者：
Sirotkin, K