Dokal I, Bungey J, Williamson P, Oscier D, Hows J, Luzzatto L
Department of Haematology, Royal Postgraduate Medical School, UK.
Blood. 1992 Dec 15;80(12):3090-6.
Dyskeratosis congenita (DC) is a rare inherited disorder characterized by bone marrow failure, dystrophic changes in the skin and mucous membranes, and a predisposition to malignancy. The DC locus has been mapped to Xq28. The primary defect responsible for this disease remains unknown. We have studied four patients with this disease, three from one family and one from another. In all four patients, primary skin fibroblast cultures were abnormal both in morphology (polygonal cell shape, ballooning, and dendritic-like projections) and in growth rate (doubling time about twice normal). Fibroblast survival studies using four clastogens (bleomycin, diepoxybutane, mitomycin-c, and 4-nitroquinoline-1-oxide) and gamma radiation showed no significant difference between DC and normal fibroblasts. Cytogenetic studies performed on peripheral blood lymphocytes showed no difference between DC and normal lymphocytes with or without prior incubation with clastogens. However, bone marrow metaphases from one of three patients and fibroblasts from two of four patients (who were the eldest of the 4) showed numerous unbalanced chromosomal rearrangements (dicentrics, tricentrics, and translocations) in the absence of any clastogenic agents. Cell-specific differences and a higher rate of chromosomal rearrangements in the older patients appear to correlate with the clinical evolution of the disease. These findings suggest that the DC defect predisposes DC cells to developing chromosomal rearrangements.
先天性角化不良（DC）是一种罕见的遗传性疾病，其特征为骨髓衰竭、皮肤和黏膜的营养不良性改变以及易患恶性肿瘤。DC基因座已被定位到Xq28。导致这种疾病的主要缺陷仍然未知。我们研究了4例患有这种疾病的患者，其中3例来自一个家族，1例来自另一个家族。在所有4例患者中，原代表皮成纤维细胞培养物在形态（多角形细胞形状、气球样变和树突状突起）和生长速率（倍增时间约为正常的两倍）方面均异常。使用四种致裂剂（博来霉素、1,4 - 丁二醇二缩水甘油醚、丝裂霉素 - c和4 - 硝基喹啉 - 1 - 氧化物）以及γ射线进行的成纤维细胞存活研究表明，DC成纤维细胞与正常成纤维细胞之间没有显著差异。对外周血淋巴细胞进行的细胞遗传学研究表明，无论是否预先用致裂剂孵育，DC淋巴细胞与正常淋巴细胞之间均无差异。然而，3例患者中的1例的骨髓中期细胞以及4例患者中的2例（这2例是4例患者中年龄最大的）的成纤维细胞在没有任何致裂剂的情况下显示出大量不平衡的染色体重排（双着丝粒、三着丝粒和易位）。老年患者中细胞特异性差异和更高的染色体重排率似乎与疾病的临床进展相关。这些发现表明，DC缺陷使DC细胞易于发生染色体重排。
