一个先天缺牙家系的基因突变及病例对照研究

目的：探讨非综合征型多数牙先天缺失患者的人类成对盒基因9(PAX9)、同源盒基因1(MSX1)、中轴抑制蛋白2(AXIN2)突变位点,为该疾病的病因学研究提供依据。方法对该例患者及其家庭成员进行全身系统检查、口腔专科检查(含拍摄曲面断层片)及家系调查；抽取外周静脉血,提取基因组DNA,采用聚合酶链式反应( PCR)扩增PAX9基因的外显子1、2、3、4,MSX1基因外显子1、2及AXIN2基因外显子2、3、4、5、6、7、8、9、10、11,通过对分段PCR纯化产物进行测序,并结合系谱图进行基因突变分析。同时,通过病例-对照实验(先天缺牙组50例,健康对照组100例)对突变位点AXIN2G1807C与先天缺牙的相关性进行分析。结果先证者的祖母和外祖父为兄妹关系。口内检查以及曲面断层片发现先证者为无牙牙合,仅见左侧下颌升支处有一阻生牙影像,其余家庭成员牙齿数目发育正常。均未合并其他组织器官的先天发育异常。先证者及部分表型正常者分别发现3个已知突变位点,分别为AXIN2外显子6第1365位A变为 G ( rs9915936),外显子7第1807位 G 变为 C (rs145353986)以及外显子8第2062位 C 变为 T ( p. Leu688Leu)。 PAX9、MSX1未见异常。病例组和对照组间AXIN2G1807C的基因频率和基因型频率差异无统计学意义。结论 AXIN2c.2062C>T突变可能是导致中国人群非综合征型多数牙缺失的危险因素之一。 AXIN2c.1807G>C与此类疾病之间不存在明显的相关性。

Gene mutations in a Chinese family associated with oligodontia:A case-control study

Objective To investigate the mutation characteristics of paired box homeotic gene 9 ( PAX9 ) , muscle segment homeobox gene 1 ( MSX1 ) and Axis inhibition protein 2 ( AXIN2 ) of patients with congenital oligodontia so as to understand the etiology and mechanism. Methods The proband and his family members from an ethnic Han family underwent complete physical and oral examinations ( including panoramic radiograph) and received ret-rospective review. Blood samples were collected and polymerase chain reaction ( PCR) was taken. Mutation analy-sis was employed in exon1 ,2 ,3 ,4 of PAX9 , exon1 ,2 of MSX1 and exon 2 ,3 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 of AXIN2 cod-ing regions. A case-control study on 50 subjects with sporadic tooth agenesis ( cases) and 100 healthy controls was performed, which genotyped a novel AXIN2 gene polymorphism (G1807C). Results The patrilineal grandmother and the maternal grandfather of the proband were found siblings. The proband lacked all teeth except an impacted tooth in the left angulus mandibulae. Other family members maintained normal dentitions. No abnormalities were revealed by clinical examination of the family members, including orofacial cleft, ectodermal abnormalities of hair, skin and sweat glands. Three known AXIN2 gene variants, c. 1365A > G ( rs9915936 ), c. 1807G > C (rs145353986) and c. 2062C>T (p. Leu688Leu) were identified in the proband and some of the family members. No mutation was found in PAX9 and MSX1 . No significant difference was found in the allele and genotype frequen-cies of the novel variant between the subjects and controls. Conclusion Our findings may imply that the AXIN2 c. 2062C>T is a risk factor for congenital oligodontia in the Chinese population and there is no significant associa-tion between c. 1807G>C and congenital oligodontia.