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

点击翻译按钮获取中文摘要

<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.