一个单纯性先天缺牙家系的临床及基因突变分析

目的探讨多数牙先天缺失患者的人类成对盒基因（PAX9）和肌节同源盒基因（MSX1）突变位点，为该疾病的病因学研究提供依据。方法对于该例患者与部分正常家庭成员进行口内检查及家系调查，取研究模型测量其牙冠宽度，并与正常值比较。拍摄曲面断层片和头颅侧位片进行头影测量分析，对比颅面形态和错畸形类型及特点。从静脉血中提取DNA，根据PAX9和MSX1的全序列设计引物，采用聚合酶链式反应（PCR）扩增PAX9基因的外显子1、2、3、4及MSX1基因外显子1、2，而后通过对分段PCR纯化产物的测序，并结合系谱进行突变分析。结果患者伴有牙齿形态畸形，与中国人正常值相比较，牙冠宽度较小。头影测量分析结果提示先证者在骨面型及颌骨形态等方面无明显遗传倾向。基因筛查结果显示先证者及其母亲的PAX9外显子3第718位点上由G变为C，属错义突变，导致与之对应的第240位氨基酸由丙氨酸变为脯氨酸；MSX1未见突变。结论多数牙先天缺失可能与PAX9基因外显子3的第718位点上的错义突变有关。

Analysis of clinical features and mutation associated with oligodontia

Objective To investigate the mutation characteristics of paired box homeotic gene 9(PAX9)and muscle segment homeobox gene 1(MSX1)of patients with congenital oligodontia.Methods Clinical manifestations were recorded by taking complete oral examinations in patients with congenital nonsyndromic oligodontia and some of his normal family members.Pedigree information was confirmed by extended interviews and a pedigree was constructed.Inheritance mode and clinical features were analyzed.Assessment of crown width compared to normal value of crown width in Chinese people was based on the registrations and measurements of study cast.Comparison of craniofacial form,malocclusion types and characteristics were conducted via cephalometric analysis by taking lateral cephalometric radiographics.Venous blood samples were collected and DNA was extracted from leukocytes.DNA sequencing and mutation analysis were analyzed in exon 1,2,3,4 of PAX9 and exon 1,2 of MSX1 coding region by polymerase chain reaction(PCR).Results The teeth shape abnormality of the patient was noticed by a measured smaller crown width compared to normal values of crown width in Chinese people.The result of cephalometric analysis indicated no obvious inherited tendency in the proband in terms of facial osseo type and jaw bone pattern.One mutation was found in the proband and his mother in exon 3 of PAX9,the missense mutation G718C causing a conservative change A240P was present.Mutation was not found in MSX1.Conclusion These findings suggest that the missense mutation G718C in exon 3 of PAX9 is likely the cause of oligodontia.