Int J Stomatol

Int J Stomatol ›› 2023, Vol. 50 ›› Issue (2): 224-229.doi: 10.7518/gjkq.2023039

• Reviews • Previous Articles     Next Articles

Research progress on the clinical characteristics of Axenfeld-Rieger syndrome and the pathogenic mechanisms of paired-like homeodomain transcription factor 2 mutations

Wang Jingyan(),Qin Man,Wang Xin.()   

  1. Dept. of Pediatric Dentistry, School and Hospital of Stomatology, Peking University, Beijing 100081, China
  • Received:2022-07-13 Revised:2022-10-10 Online:2023-03-01 Published:2023-03-14
  • Contact: Xin. Wang E-mail:jenkins_1211@163.com;pkusswangxin@bjmu.edu.cn

RichHTML

23

PDF (PC)

393

Abstract:

Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disease, which usually presents eye and oral and maxillofacial developmental defects. Paired like home domain transcription factor 2 (PITX2) is one of the identified candidate pathogenic genes of ARS, and it plays an important role in regulating craniofacial and dental development. At present, most of the known ARS patients with PITX2 mutations have a wide variety of dental and (or) craniofacial abnormalities. Hypodontia, microdontia, hypoplasia of the enamel are the frequently detecteddental manifestations in patients with ARS. Facial abnormalities usually occur in the midface, including maxillary retraction and a broad flat nasal root and so on. This article aimed to review the oral related clinical characteristics of patients with ARS and the pathogenic mechanisms of PITX2 mutations, so as to provide more clues and information for the clinical and molecular diagnosis and comprehensive treatment of such patients.

Key words: Axenfeld-Rieger syndrome, paired-like homeodomain transcription factor 2 gene, tooth, maxillofacial region, pathogenic mechanism

CLC Number: 

  • R 782

TrendMD: 
1 Seifi M, Walter MA. Axenfeld-Rieger syndrome[J]. Clin Genet, 2018, 93(6): 1123-1130.
2 Souzeau E, Siggs OM, Pasutto F, et al. Gene-speci-fic facial dysmorphism in Axenfeld-Rieger syndrome caused by FOXC1 and PITX2 variants[J]. Am J Med Genet A, 2021, 185(2): 434-439.
3 Chrystal PW, Walter MA. Aniridia and Axenfeld-Rieger syndrome: clinical presentations, molecular genetics and current/emerging therapies[J]. Exp Eye Res, 2019, 189: 107815.
4 Wang X, Liu X, Huang LQ, et al. Mutation survey of candidate genes and genotype-phenotype analysis in 20 southeastern Chinese patients with Axenfeld-Rieger syndrome[J]. Curr Eye Res, 2018, 43(11): 1334-1341.
5 Fournier BP, Bruneau MH, Toupenay S, et al. Patterns of dental agenesis highlight the nature of the causative mutated genes[J]. J Dent Res, 2018, 97(12): 1306-1316.
6 Perre PV, Seco CZ, Patat O, et al. 4q25 microdeletion encompassing PITX2: a patient presenting with tetralogy of Fallot and dental anomalies without o-cular features[J]. Eur J Med Genet, 2018, 61(2): 72-78.
7 Agarwal P, Jain K, Sandesh S, et al. Axenfeld-Rieger syndrome: rare case presentation and overview[J]. J Maxillofac Oral Surg, 2020, 19(3): 364-369.
8 Madissoon E, Jouhilahti EM, Vesterlund L, et al. Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos[J]. Sci Rep, 2016, 6: 28995.
9 Hendee KE, Sorokina EA, Muheisen SS, et al. PITX2 deficiency and associated human disease: insights from the zebrafish model[J]. Hum Mol Genet, 2018, 27(10): 1675-1695.
10 Tran TQ, Kioussi C. Pitx genes in development and disease[J]. Cell Mol Life Sci, 2021, 78(11): 4921-4938.
11 French CR. Mechanistic insights into Axenfeld-Rie-ger syndrome from zebrafish foxc1 and pitx2 mutants[J]. Int J Mol Sci, 2021, 22(18): 10001.
12 Schubert FR, Singh AJ, Afoyalan O, et al. To roll the eyes and snap a bite-function, development and evolution of craniofacial muscles[J]. Semin Cell Dev Biol, 2019, 91: 31-44.
13 St Amand TR, Zhang Y, Semina EV, et al. Antagonistic signals between BMP4 and FGF8 define the expression of Pitx1 and Pitx2 in mouse tooth-for-ming anlage[J]. Dev Biol, 2000, 217(2): 323-332.
14 Liu W, Selever J, Lu MF, et al. Genetic dissection of Pitx2 in craniofacial development uncovers new functions in branchial arch morphogenesis, late aspects of tooth morphogenesis and cell migration[J]. Development, 2003, 130(25): 6375-6385.
15 Jumlongras D, Lachke SA, O’Connell DJ, et al. An evolutionarily conserved enhancer regulates Bmp4 expression in developing incisor and limb bud[J]. PLoS One, 2012, 7(6): e38568.
16 Balic A, Thesleff I. Tissue interactions regulating tooth development and renewal[J]. Curr Top Dev Biol, 2015, 115: 157-186.
17 Chen Y, Wang Z, Lin C, et al. Activated epithelial FGF8 signaling induces fused supernumerary incisors[J]. J Dent Res, 2022, 101(4): 458-464.
18 Liu W, Selever J, Murali D, et al. Threshold-specific requirements for Bmp4 in mandibular development[J]. Dev Biol, 2005, 283(2): 282-293.
19 Yu WJ, Sun Z, Sweat Y, et al. Pitx2-Sox2-Lef1 interactions specify progenitor oral/dental epithelial cell signaling centers[J]. Development, 2020, 147(11): dev186023.
20 Sweat YY, Sweat M, Yu W, et al. Sox2 controls periderm and rugae development to inhibit oral adhesions[J]. J Dent Res, 2020, 99(12): 1397-1405.
21 Hassed SJ, Li SB, Xu WH, et al. A novel mutation in PITX2 in a patient with axenfeld-rieger syndrome[J]. Mol Syndromol, 2017, 8(2): 107-109.
22 Intarak N, Theerapanon T, Ittiwut C, et al. A novel PITX2 mutation in non-syndromic orodental anomalies[J]. Oral Dis, 2018, 24(4): 611-618.
23 Li X, Venugopalan SR, Cao HJ, et al. A model for the molecular underpinnings of tooth defects in A-xenfeld-Rieger syndrome[J]. Hum Mol Genet, 2014, 23(1): 194-208.
24 Vadlamudi U, Espinoza HM, Ganga M, et al. PITX2, beta-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter[J]. J Cell Sci, 2005, 118(Pt 6): 1129-1137.
25 Qiu M, Bulfone A, Martinez S, et al. Null mutation of Dlx-2 results in abnormal morphogenesis of pro-ximal first and second branchial arch derivatives and abnormal differentiation in the forebrain[J]. Genes Dev, 1995, 9(20): 2523-2538.
26 Espinoza HM, Cox CJ, Semina EV, et al. A molecular basis for differential developmental anomalies in Axenfeld-Rieger syndrome[J]. Hum Mol Genet, 2002, 11(7): 743-753.
27 Fan ZZ, Sun SC, Liu HC, et al. Novel PITX2 mutations identified in Axenfeld-Rieger syndrome and the pattern of PITX2-related tooth agenesis[J]. Oral Dis, 2019, 25(8): 2010-2019.
28 Seifi M, Walter MA. Accurate prediction of functional, structural, and stability changes in PITX2 mutations using in silico bioinformatics algorithms[J]. PLoS One, 2018, 13(4): e0195971.
29 Amendt BA, Sutherland LB, Semina EV, et al. The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities[J]. J Biol Chem, 1998, 273(32): 20066-20072.
30 Quentien MH, Vieira V, Menasche M, et al. Truncation of PITX2 differentially affects its activity on physiological targets[J]. J Mol Endocrinol, 2011, 46(1): 9-19.
31 Zhang F, Zhang LS, He L, et al. A PITX2 splice-site mutation in a family with Axenfeld-Rieger syndrome leads to decreased expression of nuclear PITX2 protein[J]. Int Ophthalmol, 2021, 41(4): 1503-1511.
32 Priston M, Kozlowski K, Gill D, et al. Functional analyses of two newly identified PITX2 mutants reveal a novel molecular mechanism for Axenfeld-Rieger syndrome[J]. Hum Mol Genet, 2001, 10(16): 1631-1638.
33 秦满. 儿童口腔科临床病例解析[M]. 北京: 人民卫生出版社, 2021.
Qin M. Clinical cases in pediatric dentistry[M]. Beijing: People’s Medicul Publishing House, 2021.
34 Bender CA, Koudstaal MJ, van Elswijk JF, et al. Two cases of axenfeld-rieger syndrome, report of the complex pathology and treatment[J]. Cleft Pa-late Craniofac J, 2014, 51(3): 354-360.
35 Siddiqui HP, Sennimalai K, Samrit VD, et al. Adjunctive orthodontic therapy for prosthetic rehabilitation in a growing child with Axenfeld-Rieger syndrome: a case report[J]. Spec Care Dentist, 2021, 41(3): 423-430.
36 Dressler S, Meyer-Marcotty P, Weisschuh N, et al. Dental and craniofacial anomalies associated with axenfeld-rieger syndrome with PITX2 mutation[J]. Case Rep Med, 2010, 2010: 621984.
37 Pirih FQ, Casarin M, Perussolo J, et al. Rieger syndrome: rehabilitation with dental implants[J]. Clin Adv Periodontics, 2019, 9(4): 172-176.
[1] Wang Jingnan,Deng Shuli.. Root dysplasia of teeth: a review [J]. Int J Stomatol, 2023, 50(6): 639-645.
[2] Wang Luodan,Fan Hong. Morphological characteristics of sella turcica and its relationship with malocclusion [J]. Int J Stomatol, 2023, 50(6): 653-660.
[3] Huang Yuanhong,Peng Xian,Zhou Xuedong.. Progress in research into the effect of Rhizoma Drynariae on the treatment of bone-related diseases in the oral cavity [J]. Int J Stomatol, 2023, 50(6): 679-685.
[4] Wang Renyi,Zhao Chengzhi,Pan Jian.. Research progress on the effects of prophylactic antibiotics on postoperative complications during the perioperative period of tooth extraction [J]. Int J Stomatol, 2023, 50(5): 558-565.
[5] Liu Yuntong,Liu Chang,Gao Lichao,Luo Yuxue,Cao Yubin,Hua Chengge.. Research progress on the postoperative inferior alveolar neurosensory disturbance [J]. Int J Stomatol, 2023, 50(4): 479-484.
[6] Huang Dingming, Zhang Lan, Man Yi. Biologic bases of nature tooth-related maxillary sinus floor elevation [J]. Int J Stomatol, 2023, 50(3): 251-262.
[7] Zhao Yali,Wang Zhi,Gao Yang,Xin Pengfei,Zhang Kuanshou,Liu Qingmei. Research progress on the application of KTiOPO4 laser in tooth bleaching [J]. Int J Stomatol, 2023, 50(2): 195-202.
[8] Zhao Manzhu,Song Jinlin. Research progress on expression distribution and regulation mechanism of clock genes in tooth development [J]. Int J Stomatol, 2022, 49(4): 380-385.
[9] Pang Yu,Liu Xian,Wang Liao. Application of digital template in the extraction of embedded supernumerary tooth [J]. Int J Stomatol, 2022, 49(4): 448-452.
[10] Zhao Zhe,Wang Fu,Zheng Xiuli,An Na,Chen Jihua.. Research progress on measuring methods of tooth movement under functional load [J]. Int J Stomatol, 2022, 49(3): 362-366.
[11] Guo Ziyuan,Chang Xiao,Han Kaifang,Zhang Xizhong. Low-level laser therapy for acceleration of fixed orthodontic tooth movement: a systematic review and meta-analysis [J]. Int J Stomatol, 2022, 49(2): 163-172.
[12] An Ning,Li Jiao,Mei Zhidan. Research progress on the osteoprotegerin/receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand signaling pathway of tooth eruption [J]. Int J Stomatol, 2022, 49(1): 116-120.
[13] Dong Xu,Xu Xin. Research progress on cracked tooth [J]. Int J Stomatol, 2021, 48(6): 668-674.
[14] Gao Huihui,Deng Shuli,He Xinmin,Hu Ji,an. Evaluation of pulp status and selection of treatment in young permanent teeth after trauma [J]. Int J Stomatol, 2021, 48(6): 675-682.
[15] Li Yuan-yuan,Chen Junyu,Cai He,Wan Qianbing. Effects of parathyroid hormone and parathyroid hormone-related peptide on hard dental tissue formation [J]. Int J Stomatol, 2021, 48(6): 703-710.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[7] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[8] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[9] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[10] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .