进行性骨干发育不全患者TGFβ1基因R218H突变的检测

摘要

目的 Camurati-Engelmann病(Camurati-Engelmann disease, CED),又称进行性骨干发育不全(progressive diaphyseal dysplasia, PDD),是一种罕见的常染色体显性遗传病.该病临床表现以四肢肌肉萎缩、步态摇摆、四肢酸痛、第二性征发育不良为特征,影像学表现为四肢长管状骨对称性皮质增厚、骨干增粗呈梭形和髓腔狭窄,但不侵犯骨端或骨骺.该病由TGFβ1基因突变导致,迄今国际上已发现10种突变.作者对1例中国进行性骨干发育不全患者进行TGFβ1基因的突变位点检测. 方法 应用变性高效液相色谱技术对TGFβ1基因全部7个外显子及其外显子～内含子边界进行分析,对变性高效液相色谱技术显示可能存在突变的外显子进行DNA直接测序. 结果 在TGFβ1基因第4外显子发现错义突变R218H.此突变在2000年由日本学者首次报道. 结论 该突变的发现为下一步的治疗和遗传咨询提供依据.%Objective To identify the mutation in transforming growth factor-β1 gene (TGFβ1) in a Chinese patient with Camurati-Engelmann disease(CED). Methods Denaturing high-performance liquid chromatography (DHPLC) analysis was performed on the whole seven coding exons and exon-intron boundaries, then the mutation was identified by direct sequencing. Results Mutation screening of TGFβ1 in this patient revealed a heterozygous missense mutation R218H in exon 4. Conclusion The identification of the mutation could provide essential data for subsequent therapy and genetic counseling.