CAJ | 학술논문

目的探讨锁骨颅骨发育不全(CCD)二家系的临床和影像学特点,并检测其致病基因CBFA1的突变情况.方法首先对2个CCD家系先证者及其成员进行详细的病史采集和体格检查,并利用x线及CT检查全面了解患者的全身骨骼发育情况;然后收集受试者外周静脉血,提取基因组DNA,PCR扩增CBFA1基因的全部外显子及其剪接区,检测上述2个CCD家系CBFA1基因突变.结果 (1)锁骨颅骨发育不全的临床表现有囟门闭合延迟或不闭合,颅面特殊,牙萌发过迟、多生牙以及肩窄等;x线及CT表现主要为:颅顶膨隆或下陷,囟门未闭,颅缝增宽,多发缝间骨,颅底相对较窄,蝶骨短、蝶窦小,锁骨发育不全,牙齿发育不良以及其他骨骼发育不全表现;(2)在家系1患病成员CBFA1基因第7外显子发现了一个新的错义突变即c.1259C＞T[p.T420I];在家系2患病成员CBFA1基因第2外显子发现了一个无义突变即c.577C＞T[p.R193X],该突变在中国CCD患者中首次检出.结论 (1)CCD的临床及影像学特点为囟门闭合迟缓或不闭合,特殊的颅面特征,锁骨发育不良以及牙齿发育不良,等;(2)发现了一个新的CBFA1基因突变和一个在中国CCD患者中首次检出的CBFA1基因突变,为CCD致病基因的突变位点数据库增添了新的内容.
목적 탐토쇄골로골발육불전(CCD)이가계적림상화영상학특점,병검측기치병기인CBFA1적돌변정황.방법 수선대2개CCD가계선증자급기성원진행상세적병사채집화체격검사,병이용x선급CT검사전면료해환자적전신골격발육정황;연후수집수시자외주정맥혈,제취기인조DNA,PCR확증CBFA1기인적전부외현자급기전접구,검측상술2개CCD가계CBFA1기인돌변.결과 (1)쇄골로골발육불전적림상표현유신문폐합연지혹불폐합,로면특수,아맹발과지、다생아이급견착등;x선급CT표현주요위:로정팽륭혹하함,신문미폐,로봉증관,다발봉간골,로저상대교착,접골단、접두소,쇄골발육불전,아치발육불량이급기타골격발육불전표현;(2)재가계1환병성원CBFA1기인제7외현자발현료일개신적착의돌변즉c.1259C＞T[p.T420I];재가계2환병성원CBFA1기인제2외현자발현료일개무의돌변즉c.577C＞T[p.R193X],해돌변재중국CCD환자중수차검출.결론 (1)CCD적림상급영상학특점위신문폐합지완혹불폐합,특수적로면특정,쇄골발육불량이급아치발육불량,등;(2)발현료일개신적CBFA1기인돌변화일개재중국CCD환자중수차검출적CBFA1기인돌변,위CCD치병기인적돌변위점수거고증첨료신적내용.
Objective Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor-encoding gene, core binding factor α1 (CBFA1). Over 90 mutations in CBFA1 gene have been published to date in 500 independent cases of CCD, including missense mutations, deletions, insertions, frameshift, and splice mutations. However,mutational screening of the CBFA1 gene is still far from saturation, and more novel mutations will be identified to enrich the insights into the molecular basis for the pathogenesis of CCD. The aim of this study was to explor the clinical and imageological features and detect the mutations of CBFA1 gene in two CCD families. Method In this study, the clinical features were investigated in two CCD families, radiological and CT examinations regarding osseous malformation were carried out over the entire body of these patients with CCD. Blood (2 ml ) was drawn from all affected individuals, unaffected family members and one hundred unrelated normal controls, Genomic DNA was extracted from whole blood with PureGene DNA extraction kit and PCR was performed with eight pairs of PCR primers for exons 0 to 7 of the CBFA1 gene.The mutations of CBFA1 gene were screened in these two CCD families. Result ( 1 ) The clinical features of patients with CCD include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. X-ray and CT examination showed the bulging calvarium, patent fontanelles, wide cranial sutures, multiple Wormian bones, dental dysplasia or aplasia of clavicles. (2) Two mutations were identified, one is novel missense mutation (c. 1259C > T[p. T420I] ) in CBFA1 gene exon 7,other (c. 577C > T[p. R193X] ) was reported in Chinese cases with CCD for the first time. Conclusion (1) The clinical and imageological features of patients in two CCD families include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies.(2) The T420I and R193X mutations of CBFA1 were reported, expanding the spectrum of CBFA1 mutations causing CCD.