Tamary Hannah, Alter Blanche P
Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Pediatr Hematol Oncol. 2007 Mar;24(2):87-99. doi: 10.1080/08880010601123240.
Prompt and accurate diagnosis is required for optimal treatment and genetic counseling of patients with inherited bone marrow failure syndromes (IBMFS). However, the diverse clinical picture of these syndromes and their rareness is often associated with diagnostic difficulties. Recently, an improved diagnostic approach is possible by the cloning of many of the causative genes. Fanconi anemia (FA) patients belong to at least 12 complementation groups, of which 11 genes have been cloned. An approach combining an induced chromosomal breakage test, detection of FANCD2-L by Western blot analysis, complementation group analysis, and detailed mutation analysis enables unraveling the causative mutation in the majority of patients. With the use of such strategies, genotype/phenotype correlations in FA are evolving. In dyskeratosis congenita mutations in DCK1, TERC, and TERT genes have been identified, but mutations have been found in less than half of these patients. In patients with Shwachman-Diamond syndrome, mutations in the SBDS gene were found in approximately 90% of patients. In Diamond-Blackfan anemia the RSP19 gene is mutated in 20-25% of patients. Heterozygote ELA2 mutations are found in 60-80% of severe congenital neutropenia patients. All patients with congenital amegakaryocytic thrombocytopenia have mutations in the thrombopoietin receptor gene c-Mpl.
对于遗传性骨髓衰竭综合征（IBMFS）患者的最佳治疗和遗传咨询，需要及时准确的诊断。然而，这些综合征多样的临床表现及其罕见性常常导致诊断困难。最近，通过克隆许多致病基因，一种改进的诊断方法成为可能。范可尼贫血（FA）患者至少属于12个互补组，其中11个基因已被克隆。一种结合诱导染色体断裂试验、通过蛋白质免疫印迹分析检测FANCD2-L、互补组分析和详细突变分析的方法，能够在大多数患者中找出致病突变。通过使用这些策略，FA中的基因型/表型相关性正在不断演变。在先天性角化不良中，已鉴定出DCK1、TERC和TERT基因的突变，但在不到一半的此类患者中发现了突变。在施-戴综合征患者中，约90%的患者在SBDS基因中发现了突变。在先天性纯红细胞再生障碍性贫血中，20%-25%的患者RSP19基因发生突变。60%-80%的严重先天性中性粒细胞减少症患者存在杂合子ELA2突变。所有先天性无巨核细胞血小板减少症患者的血小板生成素受体基因c-Mpl均发生突变。
