[Clinical and image features, and identification of pathogenic gene mutation of two cleidocranial dysplasia families].
[Clinical and image features, and identification of pathogenic gene mutation of two cleidocranial dysplasia families].
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发表时间：
2010-11
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通讯作者：
Guang-xin Wang;Li-Xia Ma;Wan-feng Xu;F. Song;R. Sun
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作者：
Guang-xin Wang;Li-Xia Ma;Wan-feng Xu;F. Song;R. Sun
目的锁骨颅骨发育不良（CCD）是一种显性遗传性骨骼发育不良，由成骨细胞特异性转录因子编码基因核心结合因子α1（CBFA1）突变引起。迄今为止，已在 500 个独立 CCD 病例中发表了 90 多种 CBFA1 基因突变，包括错义突变、缺失、插入、移码和剪接突变。然而，CBFA1基因的突变筛选仍远未饱和，更多新的突变将会被发现，以丰富对CCD发病机制的分子基础的认识。本研究的目的是探讨两个CCD家系的临床和影像特征并检测CBFA1基因的突变情况。方法本研究调查了两个CCD家系的临床特征，并对这些CCD患者的全身进行了骨畸形的放射学和CT检查。从所有受影响的个体、未受影响的家庭成员和一百个无关的正常对照中抽取血液（2ml），使用PureGene DNA提取试剂盒从全血中提取基因组DNA，并使用八对PCR引物对CBFA1基因的外显子0至7进行PCR。在这两个CCD家系中筛选了CBFA1基因的突变情况。结果（1）CCD患者的临床特征包括囟门延迟闭合、额叶隆起、锁骨发育不良、牙齿萌出晚及其他骨骼异常。 X线及CT检查可见颅骨膨出、囟门未闭、颅骨缝宽、多发虫骨、牙齿发育不良或锁骨发育不全。 (2)鉴定出两种突变，一种是CBFA1基因外显子7的新错义突变(c.1259C>T[p.T420I])，另一种(c.577C>T[p.R193X])首次在中国CCD病例中报道。结论（1）2个CCD家系患者的临床及影像学特征包括囟门延迟闭合、额叶隆起、锁骨发育不良、牙齿萌出晚及其他骨骼异常。 (2)报道了CBFA1的T420I和R193X突变，扩大了引起CCD的CBFA1突变谱。
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 explore the clinical and image 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 image 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.