摘要
目的 探讨范可尼贫血 (Fanconianemia ,FA)的诊断及其基因亚型。方法 将 1997年和1998年我科收治的 3例FA患儿的临床表现、诊断及基因亚型进行研究。分别对 3例FA患儿的外周血淋巴细胞进行了丝裂霉素C(MMC)诱导的染色体断裂试验 ,用细胞融合和互补分析方法 ,检测FA患儿基因亚型。结果 3例患儿临床表现主要为进行性面色苍白 ,体格发育落后 ,伴先天畸形 ;外周血象示三系减少 ;骨髓象均符合再生障碍性贫血改变。外周血淋巴细胞经MMC诱导染色体断裂率、畸变率及每个畸变细胞的染色体平均断裂率均明显增高 ,确诊为FA ;经细胞融合和互补分析方法检测 3例FA患儿均为FA A亚型基因缺陷。结论 3例FA患儿的外周血淋巴细胞均对MMC异常敏感 ;FA的发病机制可能为DNA损伤所致 ;
Objective Fanconi anemia (FA) is an autosomal recessive disease characterized by dysfunction of bone marrow hematopoiesis and congenital multiple malformation. We studied the clinical manifestations and genetic subtype of 3 children with FA to support the genetic treatment of patients with FA. Methods Three children with FA seen from 1997 to 1998 in our hospital were investigated. The peripheral blood lymphocytes were collected and mitomycin C (MMC, DNA cross link agent, the concentration 100 ng/ml) induced chromosomal breakage tests were done. The genetic subtype of FA was achieved by cell fusion and complementation analysis. Results Three cases of FA were diagnosed at the age of eight years. They were all males with history of 0.5～2 years, and exhibited progressive pale, slow growth, bone marrow function failure and congenital multiple malformation. The mean rates of chromosomal breakages in the 3 cases were 6.71, 2.98 and 6.49, respectively. The aberrant rates were 100%. The mean rates of chromosomal breakage of each aberrant cell were 6.71, 5.98 and 6.49. The rates of chromosomal breakage in 3 the cases were increased with the higher concentration of MMC. The total numbers of chromosomal breakage images were 34 and 74 at the concentration of MMC 50 ng/ml and 100 ng/ml. They were much higher than those in healthy controls (0.07 and 0.11). The genetic subtype of all the 3 cases was group A gene (FANCA). Conclusion The main manifestations of FA were dysfunction of bone marrow hematopoiesis and congenital multiple malformation. Our study indicated that peripheral blood lymphocytes in FA patients were unusually sensitive to DNA cross linking agent MMC. DNA injury was a possible pathogenesis of FA. Genetic subtype may offer some valuable information for improving the treatment of the hereditary disease.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2001年第11期689-691,共3页
Chinese Journal of Pediatrics
基金
美国范可尼贫血研究基金会资助 (IFRF)
