
上海交通大学学报(医学版) ›› 2024, Vol. 44 ›› Issue (6): 687-693.doi: 10.3969/j.issn.1674-8115.2024.06.003
窦嘉琪(
), 高洁, 卞晓玲, 王凤, 代庆刚(
), 吴轶群(
)
收稿日期:2024-02-29
接受日期:2024-03-27
出版日期:2024-06-28
发布日期:2024-06-28
通讯作者:
代庆刚,电子信箱:daiqinggang@126.com。作者简介:窦嘉琪(1999—),男,博士生;电子信箱:doujiaqi2017@sjtu.edu.cn。
基金资助:
DOU Jiaqi(
), GAO Jie, BIAN Xiaoling, WANG Feng, DAI Qinggang(
), WU Yiqun(
)
Received:2024-02-29
Accepted:2024-03-27
Online:2024-06-28
Published:2024-06-28
Contact:
DAI Qinggang, E-mail: daiqinggang@126.com.Supported by:摘要:
目的·评估配对盒基因9(paired box gene 9,PAX9)突变非综合征型先天缺牙(non-syndromic tooth agenesis,NSTA)患者的牙颌面表型。方法·对2016年1月—2023年12月于上海交通大学医学院附属第九人民医院口腔第二门诊部就诊的NSTA患者进行全外显子组测序,筛查PAX9突变患者。对筛查到的患者采用曲面体层摄影片评估缺牙的位置和数目,采用X射线头影测量评估患者的牙颌面畸形情况。结果·7例PAX9突变的NSTA患者纳入研究,男性3例(42.9%),女性4例(57.1%)。患者首诊年龄7~31岁,平均(19.7±8.0)岁。7例患者均携带PAX9杂合突变,其中4例为错义突变,3例为移码突变。平均缺失恒牙(15.9±2.9)颗,上颌缺失数[(9.6±2.6)颗]略多于下颌[(6.3±2.4)颗](P=0.030)。上颌第二磨牙(100.0%)、上颌尖牙(85.7%)、下颌第二前磨牙(85.7%)为最常见的缺失位点,下颌侧切牙(14.3%)、下颌尖牙(14.3%)为最少缺失的位点。移码突变的患者缺牙数[(18.3±2.1)颗]多于错义突变[(14.0±1.8)颗](P=0.032)。X射线头影测量结果显示:PAX9突变成年患者上牙槽座角(angle sella-nasion-subspinale,SNA)、颌凸角(angle nasion-subspinale-subspinale-porion,NA-APo)和前颅底长度(sella-nasion,S-N)均明显小于正常参考范围,提示上颌后缩,前颅底矢状向发育不足;面角(frankfort horizontal plane-nasion-porion,FH-NPo)大于参考值、Y轴角(Y axis)小于参考值,提示下颌前伸;上/下牙槽座角(angle subspinale-nasion-supramental,ANB)小于参考值,提示骨性Ⅲ类错
畸形;上中切牙角(angle upper central incisor-nasion-subspinale,angle U1-NA)大于参考值,提示上中切牙唇倾;下中切牙-下颌平面角(angle lower central incisor-mandibular plane,IMPA)、下中切牙凸度(lower central incisor-nasion-supramental,L1-NB)小于参考值,提示下中切牙舌倾,上下前牙反
倾向。结论·较为全面地报道了PAX9突变NSTA患者的牙颌面表型,有利于进一步理解PAX9在人类颌面部发育中的作用。
中图分类号:
窦嘉琪, 高洁, 卞晓玲, 王凤, 代庆刚, 吴轶群. 伴有PAX9突变非综合征型先天缺牙患者的牙颌面表型研究[J]. 上海交通大学学报(医学版), 2024, 44(6): 687-693.
DOU Jiaqi, GAO Jie, BIAN Xiaoling, WANG Feng, DAI Qinggang, WU Yiqun. Dentofacial phenotype of non-syndromic tooth agenesis patients with PAX9 mutation[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(6): 687-693.
| Patient | Gender | Age/year | Nucleotide change | Amino acid change | Exon | Sub-domain | Zygosity | Type of mutation |
|---|---|---|---|---|---|---|---|---|
| 1 | Male | 19 | c.305delT | p.I102Tfs*19 | 2 | CSD | Het | Frameshift |
| 2 | Female | 13 | c.C365A | p.S122Y | 2 | CSD | Het | Missense |
| 3 | Female | 31 | c.G151A | p.G51S | 2 | NSD | Het | Missense |
| 4 | Male | 26 | c.189delG | p.G64Afs*21 | 2 | NSD | Het | Frameshift |
| 5 | Female | 23 | c.G151A | p.G51S | 2 | NSD | Het | Missense |
| 6 | Female | 19 | c.131_134del | p.Q45Yfs*39 | 2 | NSD | Het | Frameshift |
| 7 | Male | 7 | c.G337A | p.D113N | 2 | CSD | Het | Missense |
表1 PAX9 突变NSTA患者的一般信息和突变总结
Tab 1 General information and summary of NSTA patients with PAX9 mutation
| Patient | Gender | Age/year | Nucleotide change | Amino acid change | Exon | Sub-domain | Zygosity | Type of mutation |
|---|---|---|---|---|---|---|---|---|
| 1 | Male | 19 | c.305delT | p.I102Tfs*19 | 2 | CSD | Het | Frameshift |
| 2 | Female | 13 | c.C365A | p.S122Y | 2 | CSD | Het | Missense |
| 3 | Female | 31 | c.G151A | p.G51S | 2 | NSD | Het | Missense |
| 4 | Male | 26 | c.189delG | p.G64Afs*21 | 2 | NSD | Het | Frameshift |
| 5 | Female | 23 | c.G151A | p.G51S | 2 | NSD | Het | Missense |
| 6 | Female | 19 | c.131_134del | p.Q45Yfs*39 | 2 | NSD | Het | Frameshift |
| 7 | Male | 7 | c.G337A | p.D113N | 2 | CSD | Het | Missense |
图1 PAX9 突变NSTA患者的突变位点分布示意图Note: A.A.—amino acid. N-terminus, 1?5; paired DNA-binding domain (PD), 6?131; N-terminal subdomain (NSD), 6?63; linking peptide (LP), 64?81; C-terminal subdomain (CSD), 82?131; octapeptide motif (OM), 168?189.
Fig 1 Distribution of variants in NSTA patients with PAX9 mutation
图2 PAX9 突变NSTA患者的缺牙模式Note: The prevalence of missing teeth is presented as a heat map. The darker the red, the higher the frequency of missing; the darker the blue, the lower the frequency of missing. White background represent missing frequency close to the average missing frequency of all sites in the dentition (56.6%). Max—maxilla; Mand—mandible; Mo2—the second molar; Mo1—the first molar; PM2—the second premolar; PM1—the first premolar; Ca—canine; LI—lateral incisor; CI—central incisor.
Fig 2 Pattern of missing teeth in PAX9-mutated NSTA patients
| Parameter | Adult PAX9-mutated patients | Underage PAX9-mutated patients | Classical norm | |
|---|---|---|---|---|
| Patient 2 | Patient 7 | |||
| SNA/(°) | 80.5 | 79.3 | 82.8±4.1 | |
| NA-APo(convexity)/(°) | 6.0±4.4 | |||
| S-N/mm | 71.0±3.0 | |||
| FH-NPo/(°) | 85.4±3.7 | |||
| Y axis/(°) | 64.0±2.3 | |||
| ANB/(°) | 2.7±2.0 | |||
| U1-SN/(°) | 111.4±14.7 | 110.9 | 109.4 | 105.7±6.3 |
| Angle U1-NA/(°) | 22.8±5.2 | |||
| Distance U1-NA/mm | 6.6±5.1 | 5.8 | 3.7 | 5.1±2.4 |
| IMPA(L1-MP)/(°) | 96.7±6.4 | |||
| L1-NB/mm | 6.7±2.1 | |||
表2 PAX9 突变患者的X射线头影测量参数与经典正常值对比
Tab 2 Comparison between X-ray cephalometrics analysis parameters of patients with PAX9 mutation and classical norms
| Parameter | Adult PAX9-mutated patients | Underage PAX9-mutated patients | Classical norm | |
|---|---|---|---|---|
| Patient 2 | Patient 7 | |||
| SNA/(°) | 80.5 | 79.3 | 82.8±4.1 | |
| NA-APo(convexity)/(°) | 6.0±4.4 | |||
| S-N/mm | 71.0±3.0 | |||
| FH-NPo/(°) | 85.4±3.7 | |||
| Y axis/(°) | 64.0±2.3 | |||
| ANB/(°) | 2.7±2.0 | |||
| U1-SN/(°) | 111.4±14.7 | 110.9 | 109.4 | 105.7±6.3 |
| Angle U1-NA/(°) | 22.8±5.2 | |||
| Distance U1-NA/mm | 6.6±5.1 | 5.8 | 3.7 | 5.1±2.4 |
| IMPA(L1-MP)/(°) | 96.7±6.4 | |||
| L1-NB/mm | 6.7±2.1 | |||
图3 1例典型成年 PAX9 突变患者的侧位X射线头影测量片和头影测量标志点Note: S—sella; N—nasion; Or—orbitale; A—subspinale; B—supramental; Gn—gnathion; Go—gonion; Po—porion.
Fig 3 Lateral X-ray cephalometric projection and cephalometic landmarks of a typical PAX9-mutated patient
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