Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.
Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.
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DOI：
10.1093/hmg/ddq284
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发表时间：
2010-10-01
影响因子：
3.5
通讯作者：
Stone EM
中科院分区：
文献类型：
--
作者：
Schindler EI;Nylen EL;Ko AC;Affatigato LM;Heggen AC;Wang K;Sheffield VC;Stone EM
准确预测特定基因型的致病作用对于临床试验的设计和执行以及对个体患者的有意义的咨询非常重要。然而，对于许多常染色体隐性遗传疾病，很难推断个体等位基因的相对致病贡献，因为相对较少的受影响个体具有相同的两种致病变异。在本研究中，我们使用多元回归分析来估计 ABCA4 特定等位基因对患有从 Stargardt 病到色素性视网膜炎等视网膜表型的患者的致病性。该分析揭示了对视觉表型两个方面的定量等位基因效应，即视敏度 (P < 10−3) 和视野 (P < 10−7)。个别患者的视力和视野之间的不一致表明至少存在两种非 ABCA4 修饰因子。这项研究的结果将有助于发现改变 ABCA4 疾病的因素，也将有助于最佳选择新疗法临床试验的受试者。
Accurate prediction of the pathogenic effects of specific genotypes is important for the design and execution of clinical trials as well as for meaningful counseling of individual patients. However, for many autosomal recessive diseases, it can be difficult to deduce the relative pathogenic contribution of individual alleles because relatively few affected individuals share the same two disease-causing variations. In this study, we used multiple regression analysis to estimate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from Stargardt disease to retinitis pigmentosa. This analysis revealed quantitative allelic effects on two aspects of the visual phenotype, visual acuity (P < 10−3) and visual field (P < 10−7). Discordance between visual acuity and visual field in individual patients suggests the existence of at least two non-ABCA4 modifying factors. The findings of this study will facilitate the discovery of factors that modify ABCA4 disease and will also aid in the optimal selection of subjects for clinical trials of new therapies.
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DOI：
10.1083/jcb.49.2.303
发表时间：
1971-05-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Young RW
通讯作者：
Young RW
DOI：
10.1016/s0140-6736(08)61348-3
发表时间：
2008-11-22
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ennis S;Jomary C;Mullins R;Cree A;Chen X;Macleod A;Jones S;Collins A;Stone E;Lotery A
通讯作者：
Lotery A
影响因子：
5.3
作者：
Shroyer, NF;Lewis, RA;Lupski, JR
通讯作者：
Lupski, JR
感光体ABC转运蛋白ABCA4在脂质转运和Stargardt黄斑变性中的作用。
DOI：
10.1016/j.bbalip.2009.02.004
发表时间：
2009-07
影响因子：
4.8
作者：
Molday, Robert S.;Zhong, Ming;Quazi, Faraz
通讯作者：
Quazi, Faraz
影响因子：
--
作者：
Fishman, GA;Stone, EM;Hockey, RR
通讯作者：
Hockey, RR