2例多数牙先天缺失患儿及其父母的Pax9基因突变检测

目的:探讨多数牙先天缺失患者的基因突变位点.方法:从两例多数牙先天缺失患者与家庭成员的静脉血中提取DNA,在Pax9基因内设计引物,采用PCR方法扩增Pax9基因的外显子2、3、4,而后通过对分段PCR纯化产物的测序,并结合系谱进行单核甘酸多态性分析.结果:外显子3的第88、89位点上发现两个单核甘酸多态性位点(single nucleotide polymorphisms,SNPs),其中第88位为C变为T,第99位为G变为C,前者是同义突变,后者是错义突变,由丙氨酸变为脯氨酸.结论:多数牙先天缺失可能与Pax9基因外显子3的第88、89位点上的两个SNPs有关.     

广德县 2 1 34名小学生错牙合畸形的调查

对安徽省广德县城关镇所属 4所小学的 2 134名学生的牙牙合系统进行了调查 ,以了解本地区少儿错牙合畸形的患病率及错牙合类型 ,现报告如下。1　材料与方法1.1　资料　 2 134名调查对象中 ,男性 110 9人 ,女性 10 2 5人 ,年龄 7～ 14岁。1.2　方法　室内自然光线下进行检查 ,记录检查结果。1.3　错牙合标准[1] 　按其临床表现分为 :牙拥挤、个别牙错位、深覆牙合、上牙前突、反牙合、对刃牙合、开牙合。对复合型错牙合择其严重者统计。2　结果见表 1～ 3。表 1　错牙合畸形患病率Ｔａｂ .1　Ｔｈｅｐｒｅｖａｌｅｎｃｅｏｆｍａｌｏｃｃｌｕ…     

中国一少牙畸形家系MSX1基因新突变

目的 研究一个中国少牙畸形家系MSX1基因的突变情况.方法 收集先证者和部分家系成员的外周血标本,采用聚合酶链式反应(PCR)结合DNA直接双向测序的方法,检测了该家系中7例患者及7名表型正常者和100名无亲缘关系健康个体的MSX1基因突变.结果 所有患者的MSX1基因上均存在剪切突变(IVS1-2A＞G),该突变在家系正常个体及100名健康对照个体中均未发现.结论 在MSX1基因上发现的IVS1-2A＞G为一个新的剪切突变,它可能是造成该家系先天性缺牙的致病突变.     

多个乳牙滞留、恒牙缺失、小牙畸形1例

患者男 ,18岁 ,因牙列稀疏、畸形就诊。检查 :一般情况良好 ,营养中等 ,智力正常 ,头发、眉毛稀疏 ,面下 1/ 3稍短 ,唇、腭发育正常。双侧均为近中错牙合。 5 4 ,5 5 ,6 1,6 4 ,6 5 ,75 ,81,84 ,85滞留 ,无松动。 11,13,2 2 ,33,4 3为锥形牙 ,12 ,2 3,32 ,34,4 2缺失 ,牙间有散在间隙。曲面断层Ｘ线片示 :滞留乳牙根发育完整 ,无吸收 ,乳牙和缺失牙处牙槽骨中均无恒牙。追问病史 :既往身体健康 ,否认有外伤、拔牙史 ,母亲妊娠期身体健康 ,未用过影响胎儿发育的药物。家族中无类似病史。诊断 :①乳牙滞留 ;② 11,13,2 2 ,33,4 3为过小牙 ;③ …     

对1032名中学生牙颌畸形的调查

作者对12-16岁中学生1032人进行了牙颌畸形调查,对牙颌畸形的一些临床表现进行了分析,性别之间,城镇人口与农业人口之间的发病率进行了对比,对牙颌畸形的病因及防治进行了探讨,调查结果,其发病率为91.18%,以牙量骨量不调为主。     

甘肃藏族1 111名青少年错(牙合)畸形流行病学调查

为了解甘肃藏族青少年错[牙合]畸形流行病学情况，我们对甘肃省甘南藏族自治州的合作市、夏河县等地的1111名藏族中小学生进行了流行病学调查，现将结果报告如下。     

牙颌畸形矫治的适应证（1）——乳牙列期、替牙列期矫治

口腔正畸学是根据力学原理进行组织改建的学科,所用的力包括了正畸力与矫形力:正畸力--是移动牙齿的力;矫形力--是移动颌骨的力.正是力学与美学的完美结合,带给了人们健康与美丽.     

肢端肥大症导致的错(牙合)畸形分析1例

肢端肥大症与口腔疾病的联系在于当异常分泌的生长激素作用于颌骨,会使得颌骨再次发育,进而成为安氏Ⅲ类错(牙合)畸形的发病机制之一,该文报道1例以口腔错(牙合)畸形为主诉就诊,经过一系列临床分析及推断发现患者有骨代谢异常疾病的病例.     

牙颌畸形矫治的适应证（2）——恒牙期矫治

恒牙期矫治可分为恒牙列初期青少年的矫治及成年人的矫治两个阶段.早期,恒牙期矫治的主要对象是青少年;而成人正畸兴起于20世纪70年代后,是医疗技术的不断革新与人们追求美好与健康生活的体现!     

恒牙萌出的时间、顺序与错(牙合)畸形的关系

牙齿的生长发育具有一定的时间性、顺序性。在萌出时间上,乳牙的滞留或早失都会对恒牙咬合关系产生影响。特别是由于乳牙早失发生的时间、恒牙胚在颌骨内的位置不同可使继承恒牙的萌出时间发生很大变化。而且具体个体的牙齿萌出时间还会受到种族、地域等多种因素的影响。在萌出顺序上,遗传或乳、恒牙替换障碍可引起恒牙萌出顺序紊乱,并导致[牙合]关系异常和错[牙合]畸形。临床观察表明：近年来儿童恒牙萌出情况有许多新的变化。因此,认识乳、恒牙替换过程的正常规律以及可能出现的异常情况,对儿童、青少年的口腔保健乃至全身健康都有重要的意义。     

Exclusion of coding region mutations in MSX1, PAX9 and AXIN2 in eight patients with severe oligodontia phenotype

PURPOSE: This paper describes the screening of eight patients with severe oligodontia for PAX9 and AXIN2 mutations. SUBJECTS AND METHODS: Anamnestic data and a panoramic radiograph were collected to study the phenotype of eight patients with oligodontia and their first-degree relatives. A blood sample was taken for a mutational screening for PAX9 and AXIN2 mutations. RESULTS: No mutations were discovered, but a unique nucleotide change in a conserved 5' flanking region of PAX9 was revealed. Earlier screening of the same patients for MSX1 mutations also had a negative outcome. CONCLUSIONS: Considering the discrepancy between the high incidence rate of agenesis and the relatively small number of reported causative mutations in PAX9, MSX1 and AXIN2 genes, the genetic contribution to oligodontia probably is much more heterogeneous than expected so far. Therefore negative results, like the present exclusion data, should be published more often in order to get a better appreciation of the relative contribution of these specific mutations causing oligodontia. In this context the exact number of tested probands also should be mentioned at all cases. Recent evidence of PAX9-MSX1 protein interactions in odontogenesis as well as other genes and developmental factors should receive more attention.     

PAX9基因在2个新疆维吾尔族非综合征型先天缺牙家系中的表达

目的　通过对新疆维吾尔族非综合征型先天缺牙患者PAX9基因突变的检测,为维吾尔族该病发病的分子机制提供依据。方法　采集2个新疆维吾尔族非综合征型先天缺牙家系颊黏膜拭子,提取DNA,采用聚合酶链反应技术结合DNA双向测序技术对患者DNA进行检测。结果　PAX9基因外显子3的85、86位点检测出两个单核苷酸多态性（single nucleotide polymorphisms,SNPs）位点。结论　PAX9基因外显子3的85、86位点的改变可能与新疆维吾尔族非综合征型先天缺牙的发生有关。     

多数牙先天缺失可能与MSX1上的3个SNPs相关

目的:探讨多数牙先天缺失患者的MSXl基因突变位点.方法:从4个多数牙先天缺失患者与家庭部分成员、1个唇腭裂并发少数牙先天缺失的患者、1个牙列完整的对照儿童共14人的静脉血中提取DNA,在MSXl基因内设计引物,采用PCR方法扩增MSXl基因外显子1、2的编码区,而后对外显子1、2的PCR纯化产物测序,结合系游进行序列比对分析.结果:发现3个可能的单核苷酸多态性位点(single nucleotide pol-ymorphisms,SNPs).这3个SNPs均位于外显子1中,且来自不同家系的3个患者在这3个位点上同时出现杂合突变.其中,311位点由G变A,对应的密码子由编码甘氨酸的GGC变为编码天门冬氨酸的GAC,发生了错义突变;402位点由C变A,对应的密码子由CCC变为CCA,但仍编码脯氨酸,属同义突变;458位点由C变T,对应的密码子由编码丙氨酸的GCC变为编码缬氨酸的GTC,发生了错义突变.结论:多数牙先天缺失可能与MSX1基因上该3个单核苷酸多态性位点有关.     

Sequence analysis of PAX9, MSX1 and AXIN2 genes in a Chinese oligodontia family

Objectives

The goal of our research was to look into the clinical traits and genetic mutations in nonsyndromic oligodontia in a Chinese family and to gain insight into the role of mutations of PAX9, MSX1 and AXIN2 in oligodontia phenotypes.

Materials and methods

6 subjects from a family underwent complete oral examination, including panoramic radiographs. Retrospective data were reviewed and blood samples were collected. PCR primers for PAX9, MSX1, and AXIN2 were designed through the Oligo Primer Analysis Software. PCR products were purified and sequenced using the BigDye Terminator Kit and analysed by the 3730 DNA Analyzer.

Results

The proband missed 4 permanent canines, 2 permanent maxillary lateral incisors, 2 permanent mandibular lateral incisors, and 2 permanent mandibular central incisors, whilst his maternal grandfather lacked only 2 permanent mandibular central incisors. Moreover, the size of some permanent teeth appeared smaller than normal values of crown width of Chinese people. Oligodontia and abnormalities of teeth were not present in other family members. Radiographic examination showed that the proband and the rest of family members retained all germs of the third molars. There was one known mutation A240P (rs4904210) of PAX9 in the coding region in the proband and the maternal family members (II-2, II-3, and II-4), which possibly contributed to structural and functional changes of proteins. No mutations were identified in MSX1 and AXIN2.

Conclusions

Our findings may imply that the PAX9 A240P mutation is a risk factor for oligodontia in the Chinese population. A240P is likely to be a genetic cause of oligodontia though previous literature suggested it as a polymorphism only.     

Investigating the etiology of multiple tooth agenesis in three sisters with severe oligodontia

OBJECTIVES: To describe the dentofacial phenotypes of three sisters with severe non-syndromic oligodontia, to report on the mutation analysis in three genes, previously shown to cause various phenotypes of non-syndromic oligodontia and in two other suspected genes. Based on the phenotypes in the pedigree of this family, the different possible patterns of transmission are discussed. METHODS: Anamnestic data and a panoramic radiograph were taken to study the phenotype of the three sisters and their first-degree relatives. Blood samples were also taken to obtain their karyotypes and DNA samples. Mutational screening was performed for the MSX1, PAX9, AXIN2, DLX1 and DLX2 genes. RESULTS: The probands' pedigree showed evidence for a recessive or multifactorial inheritance pattern. Normal chromosomal karyotypes were found and - despite the severe oligodontia present in all three sisters - no mutation appeared to be present in the five genes studied so far in these patients. CONCLUSIONS: In the three sisters reported, their common oligodontia phenotype is not caused by mutations in the coding regions of MSX1, PAX9, AXIN2, DLX1 or DLX2 genes, but genetic factors most probably play a role as all three sisters were affected. Environmental and epigenetic factors as well as genes regulating odontogenesis need further in vivo and in vitro investigation to explain the phenotypic heterogeneity and to increase our understanding of the odontogenic processes.     

中国先天性缺失牙患者PAX9基因的新突变

目的 探讨我国先天性缺失牙患者PAX9基因突变的特点，为该病发病的分子机制研究提供依据。方法 应用聚合酶链反应．单链构象多态性(PCR-SSCP)分析方法，对4个常染色体显性遗传少牙畸形家系(共45名成员，22例患者)中的13例患者和9名健康成员、16例散发性牙齿发育不全患者以及196名健康对照者的PAX9基因进行研究。结合DNA序列分析方法，对发现异常SSCP条带的患者进行突变分析。结果 2个少牙畸形家系(家系A和家系B)的先证者出现异常SSCP条带，家系A和家系B内患者均出现与各自先证者相同的异常SSCP条带。经过DNA序列分析，发现PAX9基因第2外显子的2个新突变：碱基插入(109InsG)导致的移码突变，碱基置换(c139T)导致的错义突变。其余家系患者、散发性患者均未发现异常SSCP条带。结论 109InsG和C139T突变扩大了先天性缺失牙患者的PAX9基因突变谱，为我国先天性缺失牙的基因诊断提供依据。     

Tgf-beta1, Tgf-beta2, Tgf-beta3 and Msx2 expression is elevated during frontonasal suture morphogenesis and during active postnatal facial growth

Authors – Adab K, Sayne JR, Carlson DS, Opperman LA. Objectives – It is hypothesized that regulation of facial suture morphogenesis is similar to that of cranial sutures, with expression of similar regulatory molecules, governing suture formation and patency. The present study was designed to characterize the morphology of the frontonasal (FN) suture of the rat at different developmental stages and to investigate the presence and temporal‐spatial expression of transforming growth factor‐beta 1 (Tgf‐β1), Tgf‐β2, Tgf‐β3 and Msx2 mRNA within these structures. Setting and sample population – The Department of Biomedical Sciences at Texas A&M University System Health Science Center, Baylor College of Dentistry, Dallas, TX USA. Histological sections and RNA isolated from FN suture tissues of Sprague‐Dawley rats, aged embryonic day 16 through postnatal day 20. Method – Sections were examined after immunohistochemical staining. Gene expression was determined by densitometric analysis of RT‐PCR products run on agarose gels. Results – FN sutures develop slightly later than cranial sutures and show increased complexity over time when compared to cranial sutures. FN sutures were closely associated with the nasal capsular cartilage, with intervening layers of perichondrium and periosteum. The pattern of expression of Tgf‐βs within the FN suture tissues was similar to that seen in the cranial sutures. However, mRNA and protein of the Tgf‐βs were differentially expressed over time compared to cranial sutures. In FN sutures, Tgf‐β mRNA levels were elevated both during the period of suture morphogenesis and during active bone growth from the suture in the early postnatal period. Msx2 mRNA expression was elevated in both the prenatal and postnatal periods, similar to Tgf‐β mRNA expression. Conclusion – Tgf‐β and Msx2 are present in facial sutures similar to cranial sutures, but are differenentially expressed over time, perhaps reflecting different bone growth rates from these sutures.     

Novel missense mutations in the AXIN2 gene associated with non-syndromic oligodontia

Objective

Oligodontia, which is the congenital absence of six or more permanent teeth excluding third molars, may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. To date, mutations in EDA, AXIN2, MSX1, PAX9, WNT10A, EDAR, EDARADD, NEMO and KRT 17 are known to associate with non-syndromic oligodontia. The aim of the study was to search for AXIN2 mutations in 96 patients with non-syndromic oligodontia.

Design

We performed mutation analysis of 10 exons of the AXIN2 gene in 96 patients with isolated non-syndromic oligodontia.

Results

We identified two novel missense mutations (Exon 3 c.923C > T and Exon 11 c.2490G > C) in two patients. One mutation (c.923C > T) results in a Thr308Met substitution and the other mutation (c.2490G > C) results in a Met830Ile substitution.

Conclusions

This is the first report indicating that mutations in AXIN2 are responsible for oligodontia in the Chinese population. Our findings indicate that AXIN2 can be regarded as a candidate gene for mutation detection in individuals with non-syndromic oligodontia in the Chinese population.