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排序方式: 共有183条查询结果,搜索用时 531 毫秒
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A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16) 下载免费PDF全文
Bikash R. Pattnaik Nathaniel York Simran Brar John Chiang De‐Ann M. Pillers Elias I. Traboulsi 《Human mutation》2015,36(7):720-727
Mutations in the KCNJ13 gene that encodes the inwardly rectifying potassium channel Kir7.1 cause snowflake vitreoretinal degeneration (SVD) and leber congenital amaurosis (LCA). Kir7.1 controls the microenvironment between the photoreceptors and the retinal pigment epithelium (RPE) and also contributes to the function of other organs such as uterus and brain. Heterologous expressions of the mutant channel have suggested a dominant‐negative loss of Kir7.1 function in SVD, but parallel studies in LCA16 have been lacking. Herein, we report the identification of a novel nonsense mutation in the second exon of the KCNJ13 gene that leads to a premature stop codon in association with LCA16. We have determined that the mutation results in a severe truncation of the Kir7.1 C‐terminus, alters protein localization, and disrupts potassium currents. Coexpression of the mutant and wild‐type channel has no negative influence on the wild‐type channel function, consistent with the normal clinical phenotype of carrier individuals. By suppressing Kir7.1 function in mice, we were able to reproduce the severe LCA electroretinogram phenotype. Thus, we have extended the observation that Kir7.1 mutations are associated with vision disorders to include novel insights into the molecular mechanism of disease pathobiology in LCA16. 相似文献
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Dewi Megawati Ita M. Nainggolan Maria Swastika Susi Susanah Johanes C. Mose Alida R. Harahap 《Hemoglobin》2014,38(2):149-151
We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T?>?A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G?>?A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value. 相似文献
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Christoph Loenarz Rok Sekirnik Armin Thalhammer Wei Ge Ekaterina Spivakovsky Mukram M. Mackeen Michael A. McDonough Matthew E. Cockman Benedikt M. Kessler Peter J. Ratcliffe Alexander Wolf Christopher J. Schofield 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(11):4019-4024
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Dong Li Rebecca C. Ahrens‐Nicklas Janice Baker Vikas Bhambhani Amy Calhoun Julie S. Cohen Matthew A. Deardorff Alberto Fernández‐Jaén Benjamin Kamien Mahim Jain Fiona Mckenzie Mark Mintz Constance Motter Kirsten Niles Alyssa Ritter Curtis Rogers Maian Roifman Sharron Townshend Catherine Ward‐Melver Samantha A. Schrier Vergano 《American journal of medical genetics. Part A》2020,182(9):2058-2067
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SMARCA4 inactivating mutations cause concomitant Coffin–Siris syndrome,microphthalmia and small‐cell carcinoma of the ovary hypercalcaemic type 下载免费PDF全文
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Tschaharganeh D Ehemann V Nussbaum T Schirmacher P Breuhahn K 《Pathology oncology research : POR》2007,13(2):84-90
Elimination of protein expression using RNA interference (RNAi) significantly improves the understanding of gene function
and represents a promising technique for the treatment of diseases such as cancer and neurological disorders. Accumulating
evidence suggests the so-called interferon-independent non-specific gene silencing of short interfering RNA (siRNA); however,
its biological and functional cellular consequences are largely unidentified. We therefore analyzed the effects of different
nonsense siRNAs on characteristic bio-parameters such as cell viability, proliferation, cell cycle distribution, apoptosis,
and migration of tumor cells. All analyzed cellular aspects have been observed to be significantly affected by the presence
of siRNA in an interferon-independent manner: viability, mitosis, and motility were significantly diminished and programmed
cell death was significantly elevated. Moreover, all cell cycle stages (G0/G1-, G2/M-, and S-phase) were moderately shifted.
Together, these results support the hypothesis that siRNA, due to sequence-specific cellular consequences, modulate bio-functionality
independent of the target sequence. This phenomenon affects the design of siRNA experiments for futurein vitro but also forin vivo tests as well as for potential therapeutic and preventive strategies. Moreover, monitoring interferon response after transfection
of siRNAs is necessary but not sufficient to exclude potential off-target effects in non-diseased cells.
The study was financially supported by grants from the Deutsche Forschungsgemeinschaft (DFG; Schi 273/4-3), Dr. Mildred Scheel
Stiftung für Krebsforschung (106178 to P. Schirmacher), the Ministry of Science, Research and the Arts of Baden-Württemberg
(Az: 23-7532.22-23-12/1 to K. Breuhahn), and the Monika Kutzner Stiftung (to K. Breuhahn). 相似文献