颅骨锁骨发育不全综合征两例及基因突变分析  

Clinical and genetical study of two unrelated cases with cleidocranial dysplasia

作　　者：张丛[1] 杜娟[1] 姜艳[1] 邢小平[1] 李梅[1] 王鸥[1] 夏维波[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科国家卫生和计划生育委员会内分泌重点实验室,北京100730

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2017年第3期239-245,共7页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：国家自然科学基金面上项目(81471088);中国医学科学院医学与健康科技创新工程协同创新团队项目(2016-12M-3-003)

摘　　要：目的检测两例散发颅骨锁骨发育不全综合征(cleidocranial dysplasia,CCD)患者的RUNX2基因突变并总结归纳CCD的疾病特征、发病机制及最新研究进展。方法对两例颅骨锁骨发育不全综合征患者进行病史采集、体格检查、实验室和影像学检查。抽取患者外周静脉血,提取基因组DNA,聚合酶链式反应(polymerase chain reaction,PCR)扩增其致病基因RUNX2的8个外显子片段,进行正反向测序,检测RUNX2基因突变情况。结果两例颅骨锁骨发育不全综合征患者均具有锁骨发育不良、颅骨畸形、囟门未闭合、牙齿发育异常、身材矮小等典型的CCD临床表现。测序结果发现1例患者RUNX2基因第7外显子存在移码突变c.1126_1127del T p.F376S fs*106,翻译提前终止,导致编码的RUNX2蛋白截短;另1例患者RUNX2基因第7外显子发生无义突变c.1123C>T p.Q375X,导致其编码蛋白提前终止。结论发现CCD患者中RUNX2基因两处新突变,丰富了CCD的致病基因突变谱。Objective To investigate the clinical characteristics and mutation in RUNX2 gene in two unrelated Chinese patients with cleidocranial dysplasia （ CCD）, and to review the new research advance of CCD. Methods Clinical data of two CCD patients were collected, including clinical manifestation, biochemical parameters and radiographic characteristics. Genomic DNA was extracted from peripheral blood samples and polymerase chain reaction （PCR） was performed to amplify the RUNX2 gene. Then the PCR product was sequenced bi-directionally and compared with normal sequences in UCSC to identify the mutations. Results Both of the patients showed typical CCD phenotypes, including hypoplastic clavicles, craniofacial abnormalities, open fontanelles, dental anomalies and short stature. Mutation analysis revealed two novel heterozygous mutations in RUNX2 gene： a frameshift mutation （c. 1126_ 1127delT, p. F376S, fs ＊ 106） in patient 1 and a nonsense mutation （c. 1123C 〉T, p. Q375X） in patient 2. Conclusion Two novel mutations in RUNX2 gene were discovered in two unrelated CCD patients. The identification of these mutations further extends the mutation spectrum of RUNX2 gene.

关 键 词：颅骨锁骨发育不全 RUNX2 突变 表型 

分 类 号：R681[医药卫生—骨科学]