范可尼贫血(FA)是一种由造血干细胞缺陷引起的常染色体隐性遗传性疾病。FA的临床表现多样且复杂。FA细胞对产生链间DNA交联的试剂如丝裂霉素C(MMC)或二环氧丁烷(DEB)表现出高度的超敏反应。至少八个互补组在八个基因中存在缺陷(FANCA,FANCB,FANCC,FANCD(1),FANCD(2),FANCE,FANCF和FANCG)已通过基因分析鉴定。六个基因(对应于亚型A,C,D(2)、E,F和G)已被着色,和编码的FA蛋白在共同的细胞途径-“FA途径”中相互作用通过它调节DNA修复。FA分子机制的研究进展为FA的基因治疗提供了理论依据。使用携带正常FA基因cDNA的逆转录病毒转导的FA细胞表现出对DNA交联剂超敏反应的表型校正,比如MMC。本文对FA的临床表现和基因组成进行综述,并对编码的FA蛋白的功能进行了综述。讨论了FA患者的造血干细胞移植和基因治疗。
Fanconi anaemia (FA) is an autosomal recessive inherited disorder caused by defects in hematopoietic stem cells. The clinical manifestations of FA are diverse and complicated. FA cells display high hypersensitivity to agents which produce interstrand DNA cross-links such as mitomycin C (MMC) or diepoxybutane (DEB). At least eight complementation groups with defects in eight genes (FANCA, FANCB, FANCC, FANCD(1), FANCD(2), FANCE, FANCF and FANCG) have been identified by gene analysis. Six genes (corresponding to subtypes A, C, D(2), E, F and G) have been coloned, and the encoded FA proteins interact in a common cellular pathway - \"FA Pathway\", through which modulate DNA repair. The progress of research on FA molecular mechanism provides gene therapy of FA with theory basis. FA cells transduced with the use of retrovirus carring the normal FA gene cDNA manifestate phenotypic correction of hypersensitivity to DNA cross-linking agents, such as MMC. In this
review the clinical manifestations and gene composition of FA, and the functions of encoded FA proteins were summarized. The hematopoietic stem cell transplantation and gene therapy for FA patients were discussed.