MOLECULAR STUDIES IN TUBEROUS SCLEROSIS

多发性硬化症（TSC）是一种常染色体显性遗传疾病， 一种影响多个器官系统的高突变率 TS是 其特征在于错构瘤和错构瘤，症状可以从 良性皮肤斑至精神发育迟滞伴癫痫至早产 死亡 TSC的估计患病率为1/10，000。 TSC是 异质性障碍 1987年，遗传连锁被证明是 染色体9 q34上的TSC和ABO血型。 大约三分之一 TSC家系中的10个家系与9 q基因座连锁。 最近， 一个实验室，使用与9 q基因座明显不连锁的家族，已经表明 位于染色体16 p13的D16 S283标记与一个 大家庭的TSC。 分离9 q34 TSC基因的进展相对缓慢 主要是因为家庭的异质性。最近发现一种 第二个TSC基因座位于16 p13，包括大部分TSC基因座， 家庭，允许澄清这些问题，并应大大 加速分离9 q TSC基因的进展。 尽管TSC在六年前首次与9 q联系在一起，但可以说， 直到最近，疾病的发病部位位于一个大约 9 q34中D9 S125远端20 cM。 然而，最近的分析表明， 9号染色体TSC基因座两侧约2cM的区域 近端为DBH，远端为D9 S114。 为进一步完善 目前正在通过开发新的标记来研究TSC基因座。 随着近侧翼标记的分离，9号染色体TSC区域 可以使用脉冲场电泳和酵母人工 从新的CEPH巨噬细胞文库中分离出染色体（YAC）， 现有的YAC图书馆 TSC区域将使用 Yacs和包含TSC基因座的宇宙重叠群。 新的标记将 当产生时，该区域内包含的基因将被分离， 作为TSC候选基因进行测试。

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with a high mutation rate which affects numerous organ systems. TS is characterized by hamartomas and harmartias and symptoms can vary from benign skin macules to mental retardation with epilepsy to premature death. The estimated prevalence of TSC is 1 per 10,000. TSC is a heterogeneous disorder. In 1987 genetic linkage was demonstrated between TSC and the ABO blood group on chromosome 9q34. Approximately one third of TSC families seem to be linked to the 9q loci. More recently this laboratory, using families clearly unlinked to the 9q loci, has shown linkage between the D16S283 marker, located at chromosome 16p13, and a large group of TSC families. Progress in isolating the 9q34 TSC gene has proceeded relatively slowly primarily because of family heterogeneity. Recent identification of a second TSC loci at 16p13, which includes the majority of the TSC families, allows the clarification of these issues and should greatly accelerate progress in isolating the 9q TSC gene. Although TSC was first linked to 9q six years ago all that could be said until recently is that the disease loci lay in a region of approximately 20 cM distal to D9S125 in 9q34. Recent analyses have, however, localized the chromosome 9 TSC loci to a region of approximately 2 cM flanked proximally by DBH and distally by D9S114. Efforts to further refine the TSC loci by developing new markers are presently underway. With the isolation of close flanking markers the chromosome 9 TSC region may be mapped using pulse field electrophoresis and Yeast Artificial Chromosomes (YAC)'s isolated from the new CEPH megabase library and existing YAC libraries. The TSC region will be physically clone using Yacs and a cosmic contig encompassing the TSC locus. New markers will be generated, genes contained within the region will be isolated and tested as TSC candidate genes.