家族性锁骨颅骨发育不全的基因突变检测

Gene mutation detection in a cleidocranial dysplasia family

目的研究家族性锁骨颅骨发育不全家系的Cbfa1基因突变。方法对临床收集到的一个牙列异常、锁骨颅骨发育不全家系行外周血基因组DNA的提取,利用聚合酶链式反应,DNA直接测序检测突变。结果在该家系中每例患者均存在Cbfa1基因外显子3中的杂合性突变,即cDNA674位G>A的单碱基突变,从而使255位的精氨酸替换为谷氨酰胺(R255Q),改变了runt结构域的氨基酸序列。结论Cbfa1基因的突变是引起此家系锁骨颅骨发育不全的致病原因。突变检测的结果可用于该家系后代的产前诊断。这也是在中国人家族性锁骨颅骨发育不全患者中首次检测到的基因突变。

Objective To study gene mutation in Chinese patients with cleidocranial dysplasia. Methods A three generation family with the clinical diagnosis of cleidocranial dysplasia was investigated in present study. Genomic DNA was extracted from peripheral blood samples of each of the family members. Direct sequencing of the PCR products of the coding region of CBFA1 gene was used to identify the mutations. Results In each patient of the family, a heterozygous missense mutation, eDNA 674 G 〉 A （R225Q）, was detected in CBFA1 exon 3. The mutation changed the sequence in runt domain of the protein. Conclusions Our findings indicate that mutation in CBFA1 is responsible for the tooth agenesis and other phenotypes of cleidocranial dysplasia in this Chinese family. The mutation detection could be applied in prenatal diagnosis for the family.