Morleo M, Franco B
Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.
J Med Genet. 2008 Jul;45(7):401-8. doi: 10.1136/jmg.2008.058305. Epub 2008 May 7.
In mammals females inactivate one of the two X chromosomes during early development to achieve an equal gene dosage between sexes. This process, named X chromosome inactivation (XCI), usually occurs randomly. However, in a few instances, non-random XCI may take place, thus modulating the phenotype observed in female patients carrying mutations in X-linked genes. Different aspects related to dosage compensation contribute to explain the influences of XCI on the phenotypic variability observed in female patients. The study of two X-linked dominant male-lethal disorders, such as the microphthalmia with linear skin lesions (MLS) syndrome and the oral-facial-digital type I (OFDI) syndrome, offers the opportunity to discuss this intriguing topic. In addition, recent data on the characterisation of a murine model for OFDI provide the opportunity to discuss how differences in the XCI between Homo sapiens and Mus musculus can justify the discrepancies between the phenotypes observed in OFDI patients and the corresponding murine model.
在哺乳动物中，雌性在早期发育过程中会使两条X染色体中的一条失活，以实现两性之间基因剂量的平衡。这个过程称为X染色体失活（XCI），通常是随机发生的。然而，在少数情况下，可能会发生非随机XCI，从而调节携带X连锁基因突变的女性患者所观察到的表型。与剂量补偿相关的不同方面有助于解释XCI对女性患者表型变异性的影响。对两种X连锁显性男性致死性疾病的研究，如小眼症伴线性皮肤损害（MLS）综合征和口面指型I（OFDI）综合征，为讨论这个有趣的话题提供了机会。此外，关于OFDI小鼠模型特征的最新数据为讨论智人与小家鼠之间XCI的差异如何解释OFDI患者与相应小鼠模型中观察到的表型差异提供了机会。
