Oostra Anneke B, Nieuwint Aggie W M, Joenje Hans, de Winter Johan P
Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Anemia. 2012;2012:238731. doi: 10.1155/2012/238731. Epub 2012 May 24.
Fanconi anemia (FA) is a rare inherited syndrome with diverse clinical symptoms including developmental defects, short stature, bone marrow failure, and a high risk of malignancies. Fifteen genetic subtypes have been distinguished so far. The mode of inheritance for all subtypes is autosomal recessive, except for FA-B, which is X-linked. Cells derived from FA patients are-by definition-hypersensitive to DNA cross-linking agents, such as mitomycin C, diepoxybutane, or cisplatinum, which becomes manifest as excessive growth inhibition, cell cycle arrest, and chromosomal breakage upon cellular exposure to these drugs. Here we provide a detailed laboratory protocol for the accurate assessment of the FA diagnosis as based on mitomycin C-induced chromosomal breakage analysis in whole-blood cultures. The method also enables a quantitative estimate of the degree of mosaicism in the lymphocyte compartment of the patient.
范可尼贫血（FA）是一种罕见的遗传性综合征，具有多种临床症状，包括发育缺陷、身材矮小、骨髓衰竭以及患恶性肿瘤的高风险。到目前为止，已区分出15种基因亚型。除了X连锁的FA-B型外，所有亚型的遗传方式均为常染色体隐性遗传。根据定义，来自FA患者的细胞对DNA交联剂（如丝裂霉素C、二环氧丁烷或顺铂）高度敏感，在细胞接触这些药物后，会表现为过度生长抑制、细胞周期停滞和染色体断裂。在此，我们提供一份详细的实验室方案，用于基于全血培养中丝裂霉素C诱导的染色体断裂分析来准确评估FA诊断。该方法还能够对患者淋巴细胞区室中的嵌合程度进行定量估计。
