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

致力于在远端 Xp 上克隆精神发育迟滞基因

• 批准号: 09470185
• 负责人: MATSUO Nobutake
• 金额: $ 6.46万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470185/
• 关键词: X chromosome; Mental retardation gene; Non-specific MR; Syndromic MR; X-inactivation; Positional cloning; Exon trapping; Homologous genes

<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.

根据15例Xp22.3基因缺失型男性患者的基因表型相关性，我们将Xp22.3&gt；上的MRX基因定位在大约200kb的区域。然后，我们构建了覆盖关键区的Cosmiod/PAC重叠群，并通过定位克隆的方法鉴定了一个新基因。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，我们在四个智力正常的女性中发现了随机的X失活模式，Xp22.3的隐蔽缺失包围了临界区，从而获得了MRX基因逃脱X-切割的遗传学证据。我们根据四个智力低下家系的基因-表型相关性，将该基因分配到DXS7182和DXS7188之间约2Mb的区域。此外，我们在四名智力受损女性中发现了随机X-失活模式，Xp21.3处有一个围绕临界区的小缺失，这为MRX基因在Xp22&gt；上的MLS基因受到X-激活提供了遗传学证据。我们在一名伴有线性皮肤缺陷(MLS)和45，X/46，X.R(X)(P22q21)/46，X，del(X)(P22)的小眼炎女婴中发现了随机X-失活模式。这表明，在X染色体不活跃的细胞中，MLS基因的功能性缺失与包括智力低下在内的MLS表型的发展有关。

项目成果

Ogata T, et al.: "Hypergonadotropic hypogonadism in a 3-year-old girl with blepharophimosis, ptosis, and epicanthus inversus syndrome." Hormone Research. 50. 93-98 (1998)

Ogata T 等人：“一名 3 岁女孩患有高促性腺激素性性腺功能减退症，患有睑裂、上睑下垂和内眦赘皮综合症。”

Ogata T,et al.: "Hypergonadotropic hypogonadism in a 3-year-old girl with blepharophimosis,ptosis,and epicanthus inversus syndrome." Hormone Research. 50. 190-192 (1998)

Ogata T 等人：“一名 3 岁女孩患有高促性腺激素性性腺功能减退症，患有睑裂、上睑下垂和内眦赘皮综合症。”

Ogata T, Matsuo N.: "The Y-specific growth gene(s) : how does it promote the stature?" Journal of Medical Genetics. 34. 323-325 (1997)

Ogata T、Matsuo N.：“Y 特异性生长基因：它如何促进身高？”

Ogata T, et al.: "Microphthalmia with linear skin defects syndrome in a mosaic female infant with monosomy for the Xp22 region : molecular analyses of the Xp22 breakpoint and the X-inactivation pattern." Human Genetics. 103. 51-56 (1998)

Ogata T 等人：“Xp22 区域单体性镶嵌女婴中伴有线性皮肤缺陷综合征的小眼症：Xp22 断点和 X 失活模式的分子分析。”

Ogata T,Hasegawa T,Matsuo N.: "Further clinical model for the possible impairment of a putative lymphogenic gene (s) for Turner stigmata." Human Genetics. 99. 290 (1997)

Ogata T、Hasekawa T、Matsuo N.：“特纳圣痕推定淋巴生成基因可能受损的进一步临床模型。”