A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings.
A novel microduplication of ARID1B: Clinical, genetic, and proteomic findings.
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DOI：
10.1002/ajmg.a.38327
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发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Natowicz MR
中科院分区：
文献类型：
--
作者：
Seabra CM;Szoko N;Erdin S;Ragavendran A;Stortchevoi A;Maciel P;Lundberg K;Schlatzer D;Smith J;Talkowski ME;Gusella JF;Natowicz MR
ARID1B 的基因改变最近被认为是智力障碍最常见的孟德尔原因之一，并且与综合征和非综合征表型相关。 ARID1B 蛋白是染色质重塑复合物 SWI/SNF-A 的一个亚基，参与转录和多个下游细胞过程的调节。我们在这里报告了由于基因内重复而具有独特的 ARID1B 明显从头突变的个体的临床、遗传和蛋白质组表型。他的神经发育表型包括严重的言语/语言障碍，智商满量程得分为 78-98，学术技能水平分散，扩大了 ARID1B 突变的表型谱。 ARID1B 的单倍体不足通过 RNA 测序和定量 RT-PCR 来确定。荧光原位杂交分析支持 ARID1B 拷贝数增益的基因内定位。主成分分析揭示了受试者的淋巴母细胞蛋白质组与对照组的显着差异。在定量的 3426 个蛋白质中，与对照相比，有 1,014 个蛋白质显着上调或下调 (q<0.01)。通路分析揭示了 EIF2 和 EIF4 信号传导、蛋白质泛素化、tRNA 充电和染色体复制等经典通路的高度显着富集。网络分析揭示了以下方面的下调：（1）参与膜、细胞器和囊泡组织的细胞内成分； (2)细胞周期控制、信号转导和核蛋白输出方面； (3)泛素化和蛋白体功能； (4) mRNA合成/剪接方面。需要进一步的研究来确定 ARID1B 的体质单倍体不足导致综合征性和非综合征性发育障碍的详细分子和细胞机制。
Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication. His neurodevelopmental phenotype includes a severe speech/language disorder with full scale IQ scores 78–98 and scattered academic skill levels, expanding the phenotypic spectrum of ARID1B mutations. Haploinsufficiency of ARID1B was determined both by RNA sequencing and quantitative RT-PCR. Fluorescence in situ hybridization analysis supported an intragenic localization of the ARID1B copy number gain. Principal component analysis revealed marked differentiation of the subject’s lymphoblast proteome from that of controls. Of 3426 proteins quantified, 1,014 were significantly up- or down-regulated compared to controls (q<0.01). Pathway analysis revealed highly significant enrichment for canonical pathways of EIF2 and EIF4 signaling, protein ubiquitination, tRNA charging and chromosomal replication, among others. Network analyses revealed down-regulation of: (1) intracellular components involved in organization of membranes, organelles and vesicles; (2) aspects of cell cycle control, signal transduction and nuclear protein export; (3) ubiquitination and proteosomal function; and (4) aspects of mRNA synthesis/splicing. Further studies are needed to determine the detailed molecular and cellular mechanisms by which constitutional haploinsufficiency of ARID1B causes syndromic and non-syndromic developmental disabilities.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
DOI：
10.1002/ajmg.c.31414
发表时间：
2014-09-01
影响因子：
3.1
作者：
Santen, Gijs W. E.;Clayton-Smith, Jill
通讯作者：
Clayton-Smith, Jill
影响因子：
4.2
作者：
Azzam S;Schlatzer D;Maxwell S;Li X;Bazdar D;Chen Y;Asaad R;Barnholtz-Sloan J;Chance MR;Sieg SF
通讯作者：
Sieg SF
染色体微阵列分析的临床实施：2513例产后病例的摘要。
影响因子：
3.7
作者：
Lu, Xinyan;Shaw, Chad A.;Patel, Ankita;Li, Jiangzhen;Cooper, M. Lance;Wells, William R.;Sullivan, Cathy M.;Sahoo, Trilochan;Yatsenko, Svetlana A.;Bacino, Carlos A.;Stankiewicz, Pawel;Ou, Zhishu;Chinault, A. Craig;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.;Ward, Patricia A.
通讯作者：
Ward, Patricia A.
影响因子：
5.8
作者：
Polpitiya, Ashoka D.;Qian, Wei-Jun;Smith, Richard D.
通讯作者：
Smith, Richard D.