Towards the cloning of the mental retardation gene (s) on the distal Xp

在15例不同类型的Xp22.3基因缺失的男性患者的基因型-表型相关性的基础上，我们将该MRX基因定位在大约200 kb的区域。然后，我们构建了覆盖关键区域的cosmiod/PAC序列，并通过定位克隆方法鉴定了一个新的基因。该基因广泛表达，包括中枢神经系统，并与Y染色体上的假基因有关。此外，我们在4名智力正常的女性中发现随机x失活模式，在Xp22.3处包含关键区域的隐性缺失，从而获得MRX基因逃避x激发的遗传证据。<MRX基因在Xp2l。根据四个智力低下家族的基因型-表型相关性，我们将该基因定位在DXS7182和DXS7188之间约2mb的区域。此外，我们在4名智力受损的女性中发现了随机的x失活模式，Xp2l有小的缺失。3包含关键区域，为MRX基因受x激发提供遗传证据。我们在患有线性皮肤缺陷（MLS）的女婴中发现了随机X失活模式，45,X/46， X, r(X)(p22q21)/46， X,del(X)（p22）。这表明，在无活性的正常X染色体细胞中，MLS基因的功能性失活是导致包括智力迟钝在内的MLS表型发展的原因。

<MRX gene at Xp22.3>We localized this gene for mental retardation (MRX) to a roughly 200 kb region, on the basis of genotype-phenotype correlations in 15 male patients with various types of nullisomy for Xp22.3. Then, we constructed a cosmiod/PAC contig covering the critical region, and identified a novel gene by means of the positional cloning method. This gene is widely expressed including the central nervous system, and is associated with a pseudogene on the Y chromosome. Furthermore, we found random X-inactivation pattern in four mentally normal females with a cryptic deletion at Xp22.3 encompassing the critical region, thereby obtaining genetic evidence for the MRX gene escaping X-incativation.<MRX gene at Xp2l.3>We assigned this gene to an approximately 2 Mb region between DXS7182 and DXS7188, on the basis of genotype-phenotype correlations in four families with mental retardation. In addition, we found random X-inactivation pattern in four mentally impaired females with a small deletion at Xp2l.3 encompassing the critical region, providing genetic evidence for the MRX gene being subject to X-incativation.<MLS gene at Xp22>We identified random X-inactivation pattern in a female infant with microphthalmia with linear skin defects (MLS) and 45, X/46, X.r(X)(p22q21)/46, X,del(X)(p22). This suggests that functional nullisomy for the MLS gene in cells with inactive normal X chromosomes is responsible for the development of MLS phenotype including mental retardation.