Fahim Abigail T, Daiger Stephen P
Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, 1000 Wall Street, 48105, Ann Arbor, MI, USA.
School of Public Health, University of Texas Health Science Center, 1200 Herman Pressler Drive, RAS W-522, 77030, Houston, TX, USA.
Adv Exp Med Biol. 2016;854:325-31. doi: 10.1007/978-3-319-17121-0_43.
The expression of X-linked genes is equalized between males and females in mammalian species through X-Chromosome inactivation (XCI). Every cell in a female mammalian embryo randomly chooses one X Chromosome for epigenetic silencing at the 8-16 cell stage, resulting in a Gaussian distribution of XCI ratios with a peak at 50:50. At the tail extremes of this distribution, X-linked recessive mutations can manifest in disease in female carriers if the mutant allele is disproportionately active. The role of XCI skewing, if any, in X-linked retinal disease is still unknown, although many have speculated that such skewing accounts for phenotypic variation in female carriers of X-linked retinitis pigmentosa (XlRP). Some investigators have used clinical findings such as tapetal-like reflex, pigmentary changes, and multifocal ERG parameters to approximate XCI patches in the retina. These studies are limited by small cohorts and the relative inaccessibility of retinal tissue for genetic and epigenetic analysis. Although blood has been used as a proxy for other tissues in determining XCI ratios, blood XCI skews with age out of proportion to other tissues and may not accurately reflect retinal XCI ratios. Future investigations in determining retinal XCI ratios and the contribution of XCI to phenotype could potentially impact prognosis for female carriers of X-linked retinal disease.
在哺乳动物物种中，通过X染色体失活（XCI）实现雄性和雌性之间X连锁基因表达的均衡。雌性哺乳动物胚胎中的每个细胞在8至16细胞阶段随机选择一条X染色体进行表观遗传沉默，从而导致XCI比例呈高斯分布，峰值在50:50。在该分布的极端尾部，如果突变等位基因过度活跃，X连锁隐性突变可在女性携带者中表现为疾病。尽管许多人推测XCI偏斜与X连锁视网膜色素变性（XlRP）女性携带者的表型变异有关，但XCI偏斜在X连锁视网膜疾病中的作用（如果有的话）仍然未知。一些研究人员利用诸如毯样反射、色素变化和多焦视网膜电图参数等临床发现来估算视网膜中的XCI斑块。这些研究受到样本量小以及视网膜组织难以进行遗传和表观遗传分析的限制。尽管血液已被用作确定XCI比例时其他组织的替代物，但血液中的XCI随年龄的变化与其他组织不成比例，可能无法准确反映视网膜的XCI比例。未来在确定视网膜XCI比例以及XCI对表型的贡献方面的研究可能会对X连锁视网膜疾病女性携带者的预后产生潜在影响。
