Bock Niko C, Lenz Sarah, Ruiz-Heiland Gisela, Ruf Sabine
Department of Orthodontics, University of Giessen, Schlangenzahl 14, 35392, Giessen, Germany.
Private Practice, Lübeck, Germany.
J Orofac Orthop. 2017 Mar;78(2):112-120. doi: 10.1007/s00056-016-0056-y. Epub 2017 Feb 15.
The literature suggests an association between phenotype and causative mutation in nonsyndromic oligodontia. Thus, the present study was designed to verify this hypothesis in a consecutive cohort of patients.
All patients with nonsyndromic oligodontia who had been treated at the study center (Department of Orthodontics, University of Giessen, Germany) over the period 1986-2013 were contacted. Candidates were included only if at least one more family member had hypo- or oligodontia (i.e., without regard to the number of congenitally missing teeth). A total of 20 patients were included. After evaluating the dental status of each participant, the Tooth Agenesis Code (TAC) was applied. On this basis, a tentative diagnosis was made to predict which gene (MSX1, AXIN2, EDA, or PAX9) was likely to show mutation. Afterwards this hypothesis was confirmed or rejected by analyzing a saliva sample for mutation of the predicted gene. If confirmed, any available family members were also genetically analyzed.
Based on their TAC scores and sums, gene mutations were predicted for MXS1 in 11, AXIN2 in 3, EDA in 6, and PAX9 in none of the patients. The evaluation of MSX1 yielded variants in 4 of 11 cases, all of which were classified as nonpathogenic since they were not considered as functional mutations. The evaluation of EDA yielded a pathogenic exon-7 mutation in 2 of 6 patients, both being brothers with different TAC scores; the same mutation, which represents a novel missense mutation, was also found in other members of the same family. The evaluation of AXIN2 yielded variants in 3 of 3 cases, all of which were classified as nonpathogenic.
Our findings obtained in consecutive patients with nonsyndromic oligodontia did not reveal any clinically relevant associations between oligodontia phenotype (based on TAC) and causative mutations for nonsyndromic oligodontia.
文献表明非综合征性少牙畸形的表型与致病突变之间存在关联。因此，本研究旨在在一组连续的患者队列中验证这一假设。
联系了1986年至2013年期间在研究中心（德国吉森大学正畸科）接受治疗的所有非综合征性少牙畸形患者。仅当至少有一名其他家庭成员有牙发育不全或少牙畸形（即不考虑先天性缺失牙的数量）时，候选者才被纳入。共纳入20名患者。在评估每位参与者的牙齿状况后，应用牙齿发育不全编码（TAC）。在此基础上，做出初步诊断以预测哪个基因（MSX1、AXIN2、EDA或PAX9）可能出现突变。之后，通过分析唾液样本中预测基因的突变来证实或否定这一假设。如果得到证实，还对任何可用的家庭成员进行基因分析。
根据他们的TAC评分和总分，预测11名患者的MXS1、3名患者的AXIN2、6名患者的EDA有基因突变，而所有患者中均未预测PAX9有基因突变。对MSX1的评估在11例中有4例产生了变异，所有这些变异均被归类为非致病性，因为它们不被视为功能性突变。对EDA的评估在6例中有2例产生了致病性外显子7突变，这两名患者是兄弟，TAC评分不同；在同一家庭的其他成员中也发现了相同的突变，这是一种新的错义突变。对AXIN2的评估在3例中有3例产生了变异，所有这些变异均被归类为非致病性。
我们在连续的非综合征性少牙畸形患者中获得的研究结果并未揭示少牙畸形表型（基于TAC）与非综合征性少牙畸形的致病突变之间存在任何临床相关的关联。
