CELLULAR AND METABOLIC BASIS OF ROBERTS SYNDROME

罗伯茨综合征（RS）是一种隐性遗传的发育障碍 特征是对称的肢体减少， 生长迟缓和一些颅面畸形，包括 唇裂和腭裂 这些患者中约有一半还患有 涉及异染色质的不寻常的染色体异常，但具有正常的 核型检查时，通过常规技术。 真皮成纤维细胞 从3个这样的病人已经被证明有一些异常的 在培养中生长的特性。 其中包括增长率下降 接种率和接种效率，培养物中的早衰，增加 细胞大小、有丝分裂异常和高死亡率。 他们也是 对某些诱变剂过敏 其中一组实验旨在 确定是否从这些第一个细胞中看到的增殖缺陷 病例也将在来自较大的 这类患者的人群以及异常的严重程度 不同的病人，也许是成比例的严重程度， 综合征 无论这些特征是否发生在杂合子 还将确定承运人。 设计了第二组实验 确定综合征的代谢、细胞和分子基础， 最终找出缺陷基因。 这些 包括营养补充研究、核苷酸库研究， 分析这些细胞在细胞周期中的进展能力 一项关于它们合成RNA和蛋白质的能力的研究， 放射自显影、流式细胞术和定量视频增强 显微技术。 除了增加我们对 这种综合征，这项工作可以作为一个模型的研究， 其他畸形/生长迟缓综合征中的增殖缺陷 在用于研究药物作用机制的实验系统中， 致畸剂

Roberts syndrome (RS) is a recessively-inherited, developmental disorder characterized by symmetrical limb reductions, profound pre- and postnatal growth retardation and a number of craniofacial abnormalities including cleft lip and cleft palate. About half of these patients also have an unusual chromosome abnormality involving heterochromatin but have a normal karyotype when examined by conventional techniques. Dermal fibroblasts from 3 such patients have been shown to have a number of abnormal characteristics when grown in culture. These include decreased growth rates and plating efficiencies, premature senescence in culture, increased cell size, mitotic abnormalities and high death rates. They are also hypersensitive to certain mutagens. One set of experiments is designed to determine whether the proliferative defects seen in cells from these first cases will also be found in available strains derived from a larger population of such patients and whether the severity of the abnormalities varies between patients, perhaps in proportion to the severity of the syndrome. Whether or not these characteristics occur in heterozygous carriers will also be determined. A second set of experiments is designed to identify the metabolic, cellular and molecular bases of the syndrome and to eventually lead to the identification of the defective gene. These include nutrient supplementation studies, studies of nucleotide pools, an analysis of the ability of these cells to progress through the cell cycle and a study of their ability to synthesize RNA and protein using autoradiographic, flow cytometric and quantitative video intensification microscopic techniques. In addition to increasing our understanding of this syndrome, this work can serve as a model for the study of proliferation defects in other malformation/growth-retardation syndromes and in experimental systems used to study the mechanism of action of teratogenic agents.