Objective: To investigate the genetic instability in patients with Dyskeration congenita.
Methods: The spontaneous chromosome instability of lymphocytes from 4 DC patients, 29 FA patients and 24 healthy volunteers was assessed with comet assay. The percent of DNA in comet head (HeadDNA%）, the percent of DNA in comet tail (TailDNA%）, tail moment (TM), olive tail moment (OTM), the comet cell percentage (CCP) were compared between groups. And the results of MMC test, PNH clones and karotype were analysed additionally. The correlation between TM, OTM, CCP and the severity degree of bone marrow failure in DC group were evaluated.
Results: ①PNH clones and karotype abnormalities were not found in 4 DC patients. ②TM (6.77 ± 0.90), OTM（6.19 ± 0.80) and CCP [(46.00 ± 5.03) %] in DC were significantly higher than those in normal control group [0.61 ± 0.49, 0.66 ± 0.42, (5.91 ± 3.19)%, P<0.05], however, not distinguished from FA patients [7.81 ± 3.58, 6.65 ± 2.21, (56.03 ± 13.47) %, P ≥ 0.05]. The aberrant cell percent at the MMC concentration of 80 μg/L in DC group was significantly lower than that in FA group [(21.00 ± 3.16) % vs (31.97 ± 6.33)%, P=0.003]. ③The correlation between TM, OTM, CCP and the severity of bone marrow failure in DC group were not found (P>0.05).
Conclusion: DC patients were of significantly increased genetic instability and normal DNA repair, which was different from that in FA patients. And there was no correlation between the degree of genetic instability and the severity of bone marrow failure in DC patients presenting as aplastic anemia.
目的: 研究先天性角化不良症（DC）患者细胞遗传不稳定性、分析其可能的机制及其与造血衰竭严重程度的相关性。
方法: 应用彗星试验检测4例DC患者、29例Fanconi贫血患者和24名正常志愿者的外周血淋巴细胞，比较各组彗星头部DNA百分比（HeadDNA%）、彗星尾部DNA百分比（TailDNA%）、尾矩（TM）、Olive尾矩（OTM）和彗星细胞率（CCP），结合丝裂霉素C（MMC）试验和骨髓造血细胞常规染色体核型结果进行分析。
结果: ①4例DC患者均未发现克隆性异常染色体核型。②DC组的TM (6.77±0.90）、OTM(6.19±0.80）和CCP[（46.00±5.03）%]均明显高于正常对照组[0.61±0.49、0.66±0.42、（5.91±3.19）%]，差异均有统计学意义（P值均<0.05），与Fanconi贫血组[7.81±3.58、6.65±2.21、（56.03±13.47）%]比较差异无统计学意义（P值均≥0.05）。③在MMC 80 µg/L条件下DC组畸变细胞率明显低于Fanconi贫血组[（21.00±3.16）%对（31.97±6.33）%，P=0.003]。④DC患者的CCP、OTM、TailDNA%、TM与其外周血HGB水平和PLT、中性粒细胞绝对计数无明显相关性（P>0.05）。
结论: DC患者细胞遗传不稳定性显著增高，而DNA损伤修复机制基本正常；DC遗传不稳定程度与已经发生的造血衰竭严重程度无相关。