Ali Abdullah Mahmood, Kirby Michelle, Jansen Michael, Lach Francis P, Schulte Jennifer, Singh Thiyam Ramsing, Batish Sat D, Auerbach Arleen D, Williams David A, Meetei Amom Ruhikanta
Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Hum Mutat. 2009 Jul;30(7):E761-70. doi: 10.1002/humu.21032.
Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder characterized by aplastic anemia, cancer susceptibility and cellular sensitivity to DNA crosslinking agents. Eight FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL and FANCM) and three non-FA proteins (FAAP100, FAAP24 and HES1) form an FA nuclear core complex, which is required for monoubiquitination of the FANCD2-FANCI dimer upon DNA damage. FANCL possesses a PHD/RING-finger domain and is a putative E3 ubiquitin ligase subunit of the core complex. In this study, we report an FA patient with an unusual presentation belonging to the FA-L complementation group. The patient lacks an obvious FA phenotype except for the presence of a café-au-lait spot, mild hypocellularity and a family history of leukemia. The molecular diagnosis and identification of the FA subgroup was achieved by FA complementation assay. We identified bi-allelic novel mutations in the FANCL gene and functionally characterized them. To the best of our knowledge, this is the second reported case belonging to the FA-L complementation group.
范可尼贫血（FA）是一种罕见的常染色体隐性或X连锁疾病，其特征为再生障碍性贫血、癌症易感性以及细胞对DNA交联剂敏感。八种FA蛋白（FANCA、FANCB、FANCC、FANCE、FANCF、FANCG、FANCL和FANCM）和三种非FA蛋白（FAAP100、FAAP24和HES1）形成一个FA核核心复合物，DNA损伤时FANCD2 - FANCI二聚体的单泛素化需要该复合物。FANCL具有一个PHD/环指结构域，是核心复合物中一个推定的E3泛素连接酶亚基。在本研究中，我们报告了一名属于FA - L互补组的表现异常的FA患者。除了有一个牛奶咖啡斑、轻度细胞减少和白血病家族史外，该患者缺乏明显的FA表型。通过FA互补试验实现了FA亚组的分子诊断和鉴定。我们在FANCL基因中鉴定出双等位基因新突变并对其进行了功能表征。据我们所知，这是第二例报告的属于FA - L互补组的病例。
