八例先天性角化不良伴骨髓衰竭患儿的临床特征及基因分析

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. CONCLUSION: TINF2 and DKC1 mutations were the main genetic phenotypes in childhood DC with marrow failure patients. Androgen is effetive in some cases.