Objective: To summary clinical and genetic features of childhood dyskeratosis congenital (DC) patients with bone marrow failure.
Methods: The clinical data of 8 DC patients with bone marrow failure diagnosed between September 2010 and September 2015 were collected. Whole exons with flanking regions of the 16 telomere-related genes, including DKC1, TERC, TERT, NOP10, NHP2, TINF2 and so on, were analyzed by next generation sequence.
Results: Six males and two females were included, with a median age of 42(15-60) months. The median blood cell count at onset were as follow: WBC 3.99 (1.26-5.44) × 10(9)/L, ANC 1.11 (0.38-2.15) × 10(9)/L, RBC 2.45 (0.37-3.56) × 10(12)/L, HGB 82.5(15-127) g/L, PLT 27 (2-112) ×10(9)/L. Hypoplastic or marked hypoplastic bone marrow were seen in 6 patients. DKC1 mutiaton were indentified in 3 patients: one c.961C>A mutation, and two c.1058C>T mutation. TINF2 mutations were identified in 4 patients: c.849delC, c.844C>T, c.811C>T, c.862T>A combined c.871delA. One patient had TINF2 mutation c.848C>A combined TERT mutation c.1138C>T. DKC1 c.961C>A mutation, TINF2 c.849delC mutation and TINF2 c.871delA mutaion were not reported so far. 5 of 7 patients got better after androgen administration. During follow-up, one patient died of serious infection, the other seven patients continued the treatment.
Conclusions: TINF2 and DKC1 mutations were the main genetic phenotypes in childhood DC with marrow failure patients. Androgen is effetive in some cases.
目的: 加深对先天性角化不良（dyskeratosis congenital，DC）伴骨髓衰竭的认识。
方法: 收集2010年9月30日至2015年9月30日8例伴骨髓衰竭DC患儿的临床资料，利用二代测序技术对DKC1、TERC、TERT、NOP10、NHP2、TINF2等16种端粒相关基因进行全外显子及剪接位点测序分析。
结果: 8例DC患儿中男6例、女2例，中位发病月龄为42(15~60）个月。初诊血常规：中位WBC 3.99（1.26~5.44）×109/L，中位中性粒细胞计数1.11(0.38~2.15）×109/L，中位RBC 2.45(0.37~3.56）×1012/L，中位HGB 82.5(15~127) g/L，中位PLT 27（2~112）×109/L。8例患儿中6例骨髓增生减低或重度减低。3例患儿检出DKC1基因突变：c.961C>A 1例，c.1058C>T 2例；4例患儿检出TINF2基因突变：c.849delC、c.844C>T、c.811C>T、c.862T>A合并c.871delA各1例；1例患儿检出TINF2基因突变（c.848C>A）合并TERT基因突变（c.1138C>T）。其中DKC c.961C>A、TINF2 c.849delC、TINF2 c.871delA突变为首次报道。7例患儿口服雄激素治疗，其中5例血常规指标改善。1例患儿死于重症感染，其余7例患儿维持治疗。
结论: DC伴骨髓衰竭以TINF2突变和DKC1突变为主。雄激素治疗对部分病例有效。