IGENE(S) FOR PRIMARY CONGENITAL GLAUCOMA

原发性先天性青光眼（PCG）是一种常染色体隐性遗传疾病， 由未知的小梁发育缺陷引起的疾病 网状结构和前房角。 虽然PCG是最常见的形式， 对于婴儿期的青光眼，没有什么安全的是知道其具体的 胚胎学发病机制，尽管各种动物模型的研究。 此外，尽管已经提出了单一染色体分配， 目前还没有通过任何临床、生物化学或 分子技术 治疗主要是外科手术，成功率不一， 因为可能需要不止一次手术干预来控制 这些患者中的许多人的眼内压。 因此， 与这种情况相关的显著发病率和目前 可用的治疗方案。 研究人员将应用遗传学方法， 分离PCG基因的物理作图策略。 两 互补连锁的方法，基因作图将使用：远交 家系连锁研究的“同胞对”方法和纯合性作图。 后一种方法将利用沙特阿拉伯血统。 初始基因定位的替代策略包括：（I） 等位基因频率依赖性纯合性作图（AHM）和（ii）合并 来自受影响和未受影响个体的基因组DNA样本， 血统 其他传统映射方法将用于定位 克隆包括YAC重叠群构建、PFGE作图、眼cDNA文库 筛选和外显子捕获。 突变扫描检测方法包括 异源双链体分析，错配碱基的化学切割，SSCP分析， DGGE和直接DNA测序将检测特定的突变。 的 PCG基因的鉴定对眼和 人类发展，并有潜力提高生活质量 受影响的个人。 此外，它将使准确的 识别可能是该疾病携带者的兄弟姐妹，并具有 改变或防止破坏性视觉后果的最终能力 这种疾病在后代中的影响。

DESCRIPTION: Primary Congenital Glaucoma (PCG) is an autosomal recessive disorder caused by unknown developmental defect(s) of the trabecular meshwork and anterior chamber angle. Although PCG is the most common form of glaucoma in infancy, nothing secure is known about its specific ambryologic pathogenesis despite studies of various animal models. Furthermore, although a single chromosomal assignment has been proposed there is no method to detect carriers by any clinical, biochemical or molecular techniques. Therapy is primarily surgical with variable success, as more than one surgical intervention might be necessary to control intraocular pressure in a number of these patients. Thus, there is significant morbidity associated with both this condition and the currently available treatment options. The investigators will apply genetic an physical mapping strategies to isolate the gene(s) for PCG. Two complementary linkage approaches to gene mapping will be used: outbred family linkage studies of the "sib pair" method and homozygosity mapping. The latter approach will utilize consanguineous Saudi Arabian pedigrees. Alternative strategies for initial gene localization will include: (I) allele-frequency dependent homozygosity mapping (AHM) and (ii) pooling of genomic DNA samples from affected and unaffected individuals in single large pedigrees. Other traditional mapping approaches to be use for positional cloning include YAC contig building, PFGE mapping, eye cDNA library screening, and exon trapping. Mutation scanning detection methods including heteroduplex analysis, chemical cleavage of mismatched bases, SSCP analysis, DGGE, and direct DNA sequencing will then detect specific mutations. The identification of a PCG gene has potent implications for both ocular and human development and have the potential to improve the quality of life of the affected individuals. Further, it will enable the accurate identification of siblings who may be carriers of the condition, and has the ultimate capacity to modify or prevent the devastating visual consequences of this disorder in future generations.