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 特点是对称的肢体缩小，出生前和出生后的深度 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 异常的染色体异常，涉及异染色质，但有正常的 用常规技术检查核型。真皮成纤维细胞 从3名这样的患者被证明有一些异常 在培养中生长时的特征。其中包括增长放缓。 培养中过早衰老的比率和电镀效率提高 细胞大小、有丝分裂异常和高死亡率。他们也是 对某些诱变剂高度敏感的。其中一组实验旨在 确定细胞中出现的增殖性缺陷是否首先 病例也将在可用菌株中发现，这些菌株来自较大的 这类患者的人数以及异常的严重程度 在不同的患者之间，可能与疾病的严重程度成比例 综合症。这些特征是否出现在杂合子中 运营商也将被确定。设计了第二组实验 确定综合征的代谢、细胞和分子基础，并 最终导致对缺陷基因的鉴定。这些 包括营养补充研究，核苷酸池研究，以及 分析这些细胞在细胞周期中前进的能力 并研究了它们合成RNA和蛋白质的能力 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 本研究可为中医辨证分型的研究提供借鉴 其他畸形/生长迟缓综合征的增殖缺陷 并在用于研究其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.