Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders.
Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders.
复制标题
DOI：
10.3390/biomedicines10010160
复制
发表时间：
2022-01-12
期刊：
影响因子：
4.7
通讯作者：
Greicius MD
中科院分区：
文献类型：
--
作者：
Napolioni V;Fredericks CA;Kim Y;Channappa D;Khan RR;Kim LH;Zafar F;Couthouis J;Davidzon GA;Mormino EC;Gitler AD;Montine TJ;Schüle B;Greicius MD
我们描述了路易体谱系障碍（LBSD）患者的临床和神经病理特征，携带无义变异，c.604C >t；p.R202X，在葡萄糖脑苷酶1 （GBA）基因中。虽然这种GBA变异是戈歇病的病因，但这种突变在LBSD中的致病作用尚不清楚。对1例指标病例进行了详细的神经病理学评估，并对其他GBA p.R202X携带者进行了结构化的文献回顾。通过系统的文献检索，我们确定了另外三名携带相同GBA突变的报告受试者，包括一名疾病早期发病的帕金森病（PD）患者，一名神经病理学证实的LBSD患者，以及一名戈谢病患者的未受影响的亲属。在携带GBA p.R202X基因的受试者中，所有男性诊断为路易体痴呆，2名女性诊断为PD。GBA p.R202X在LBSD患者和家庭中的临床外显率有力地证明了该变异的致病作用，尽管在临床和病理特征上表现出显著的表型异质性。
We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher’s disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson’s disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher’s disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features.
登录
查看更多内容
影响因子：
48
作者：
Irwin, David;Grossman, Murray;Weintraub, Daniel;Hurtig, Howard I.;Duda, John E.;Xie, Sharon X.;Lee, Edward B.;Van Deerlin, Vivianna M.;Lopez, Oscar L.;Kofler, Julia K.;Nelson, Peter T.;Jicha, Gregory A.;Woltjer, Randy;Quinn, Joseph F.;Kaye, Jeffery;Leverenz, James B.;Tsuang, Debby;Longfellow, Katelan;Yearout, Dora;Kukull, Walter;Keene, C. Dirk;Montine, Thomas J.;Zabetian, Cyrus P.;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
DOI：
10.1002/mds.26359
发表时间：
2016-01
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Mata IF;Leverenz JB;Weintraub D;Trojanowski JQ;Chen-Plotkin A;Van Deerlin VM;Ritz B;Rausch R;Factor SA;Wood-Siverio C;Quinn JF;Chung KA;Peterson-Hiller AL;Goldman JG;Stebbins GT;Bernard B;Espay AJ;Revilla FJ;Devoto J;Rosenthal LS;Dawson TM;Albert MS;Tsuang D;Huston H;Yearout D;Hu SC;Cholerton BA;Montine TJ;Edwards KL;Zabetian CP
通讯作者：
Zabetian CP
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G
DOI：
10.1056/nejmoa0901281
发表时间：
2009-10-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sidransky E;Nalls MA;Aasly JO;Aharon-Peretz J;Annesi G;Barbosa ER;Bar-Shira A;Berg D;Bras J;Brice A;Chen CM;Clark LN;Condroyer C;De Marco EV;Dürr A;Eblan MJ;Fahn S;Farrer MJ;Fung HC;Gan-Or Z;Gasser T;Gershoni-Baruch R;Giladi N;Griffith A;Gurevich T;Januario C;Kropp P;Lang AE;Lee-Chen GJ;Lesage S;Marder K;Mata IF;Mirelman A;Mitsui J;Mizuta I;Nicoletti G;Oliveira C;Ottman R;Orr-Urtreger A;Pereira LV;Quattrone A;Rogaeva E;Rolfs A;Rosenbaum H;Rozenberg R;Samii A;Samaddar T;Schulte C;Sharma M;Singleton A;Spitz M;Tan EK;Tayebi N;Toda T;Troiano AR;Tsuji S;Wittstock M;Wolfsberg TG;Wu YR;Zabetian CP;Zhao Y;Ziegler SG
通讯作者：
Ziegler SG