国际口腔医学杂志

国际口腔医学杂志 ›› 2021, Vol. 48 ›› Issue (6): 718-724.doi: 10.7518/gjkq.2021095

• 综述 • 上一篇    下一篇

5种常见综合征型唇腭裂遗传学研究进展

孙嘉琳(),林岩松,石冰,贾仲林()   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院唇腭裂外科 成都 610041
  • 收稿日期:2021-01-12 修回日期:2021-06-30 出版日期:2021-11-01 发布日期:2021-10-28
  • 通讯作者: 贾仲林
  • 作者简介:孙嘉琳,硕士,Email： nkujialin@163.com
  • 基金资助:
    四川省科技厅应用基础项目重大前沿课题(2020YJ0211)

Research progress on genetics of five common syndromic subtypes of cleft lip and palate

Sun Jialin(),Lin Yansong,Shi Bing,Jia Zhonglin()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Cleft Lip and Palate Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2021-01-12 Revised:2021-06-30 Online:2021-11-01 Published:2021-10-28
  • Contact: Zhonglin Jia
  • Supported by:
    Major Frontier Issues of the Application Foundation Project of Sichuan Science and Technology Department(2020YJ0211)

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摘要：

唇腭裂是最常见的先天畸形之一。根据是否伴有全身其他部位的先天疾病,可分为非综合征型唇腭裂和综合征型唇腭裂。研究发现非综合征型唇腭裂为多因素遗传病,同时受多种遗传和环境危险因素的影响。而综合征型唇腭裂人群发病率相对较低,为单基因病,符合孟德尔遗传定律,呈明显的家族遗传性,且大多有明确的致病基因。本文将就5种发病率较高,较为常见的综合征型唇腭裂近年来遗传学方面的进展进行介绍,为将来综合征型唇腭裂遗传研究提供参考。

关键词: 综合征型唇腭裂, 致病基因, 遗传研究

Abstract:

Cleft lip and palate is one of the most common congenital malformations. On the basis of the presence of additional clinical features, it can be divided into non-syndromic cleft lip and palate and syndromic cleft lip and palate. Stu-dies have found that non-syndromic cleft lip and palate is a multi-factorial genetic disease, which is affected by a variety of genetic factors and environmental risk factors. However, syndromic cleft lip and palate is a low-incidence defect and single-gene disease. It has clear pathogenic genes and shows obvious familial transmissibility in accordance with Mendelian inheritance. This review summarises the research progress on genetics of five common syndromic subtypes of cleft lip and palate and provides reference for future genetic study on this disease.

Key words: syndromic cleft lip and palate, pathogenic gene, genetic research

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  • R782.2
[1] Dixon MJ, Marazita ML, Beaty TH, et al. Cleft lip and palate: understanding genetic and environmental influences[J]. Nat Rev Genet, 2011, 12(3):167-178.
doi: 10.1038/nrg2933
[2] Burdick AB. Genetic epidemiology and control of genetic expression in Van der Woude syndrome[J]. J Craniofac Genet Dev Biol Suppl, 1986, 2:99-105.
pmid: 3491128
[3] Burdick AB, Bixler D, Puckett CL. Genetic analysis in families with Van der Woude syndrome[J]. J Craniofac Genet Dev Biol, 1985, 5(2):181-208.
pmid: 4019732
[4] Malik S, Wilcox ER, Naz S. Novel lip pit phenotypes and mutations of IRF6 in Van der Woude syndrome patients from Pakistan[J]. Clin Genet, 2014, 85(5):487-491.
doi: 10.1111/cge.12207 pmid: 23713753
[5] Alade AA, Buxo-Martinez CJ, Mossey PA, et al. Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van der Woude syndrome[J]. Mol Genet Genomic Med, 2020, 8(8):e1355.
[6] Leslie EJ, Standley J, Compton J, et al. Comparative analysis of IRF6 variants in families with Van der Woude syndrome and popliteal pterygium syndrome using public whole-exome databases[J]. Ge-net Med, 2013, 15(5):338-344.
[7] Parada-Sanchez MT, Chu EY, Cox LL, et al. Disrupted IRF6-NME1/2 complexes as a cause of cleft lip/palate[J]. J Dent Res, 2017, 96(11):1330-1338.
doi: 10.1177/0022034517723615 pmid: 28767310
[8] Liu H, Leslie EJ, Jia ZL, et al. Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate[J]. Hum Mol Genet, 2016, 25(4):766-776.
doi: 10.1093/hmg/ddv614
[9] Kousa YA, Roushangar R, Patel N, et al. IRF6 and SPRY4 signaling interact in periderm development[J]. J Dent Res, 2017, 96(11):1306-1313.
doi: 10.1177/0022034517719870 pmid: 28732181
[10] Leslie EJ, Mancuso JL, Schutte BC, et al. Search for genetic modifiers of IRF6 and genotype-phenotype correlations in Van der Woude and popliteal ptery-gium syndromes[J]. Am J Med Genet A, 2013, 161A(10):2535-2544.
[11] Peyrard-Janvid M, Leslie EJ, Kousa YA, et al. Do-minant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development[J]. Am J Hum Genet, 2014, 94(1):23-32.
doi: 10.1016/j.ajhg.2013.11.009 pmid: 24360809
[12] Carpinelli MR, de Vries ME, Jane SM, et al. Grainy-head-like transcription factors in craniofacial deve-lopment[J]. J Dent Res, 2017, 96(11):1200-1209.
doi: 10.1177/0022034517719264 pmid: 28697314
[13] Degen M, Girousi E, Feldmann J, et al. A novel Van der woude syndrome-causing IRF6 variant is subject to incomplete non-sense-mediated mRNA decay affecting the phenotype of keratinocytes[J]. Front Cell Dev Biol, 2020, 8:583115.
doi: 10.3389/fcell.2020.00583
[14] Karbarz M. Consequences of 22q11.2 microdeletion on the genome, individual and population levels[J]. Genes (Basel), 2020, 11(9):E977.
[15] Martucciello S, Turturo MG, Bilio M, et al. A dual role for Tbx1 in cardiac lymphangiogenesis through genetic interaction with Vegfr3[J]. FASEB J, 2020, 34(11):15062-15079.
[16] Motahari Z, Maynard TM, Popratiloff A, et al. Aberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic mo-dels of 22q11.2 deletion syndrome[J]. Hum Mol Ge-net, 2020, 29(18):3081-3093.
[17] Edelmann L, Pandita RK, Morrow BE. Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome[J]. Am J Hum Genet, 1999, 64(4):1076-1086.
pmid: 10090893
[18] Shaikh TH, Kurahashi H, Saitta SC, et al. Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis[J]. Hum Mol Genet, 2000, 9(4):489-501.
pmid: 10699172
[19] Baumer A, Riegel M, Schinzel A. Non-random asynchronous replication at 22q11.2 favours unequal meio-tic crossovers leading to the human 22q11.2 deletion[J]. J Med Genet, 2004, 41(6):413-420.
pmid: 15173225
[20] McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome)[J]. Medicine (Baltimore), 2011, 90(1):1-18.
doi: 10.1097/MD.0b013e3182060469
[21] Lopez-Rivera E, Liu YP, Verbitsky M, et al. Genetic drivers of kidney defects in the DiGeorge syndrome[J]. N Engl J Med, 2017, 376(8):742-754.
doi: 10.1056/NEJMoa1609009
[22] Lin A, Ching CRK, Vajdi A, et al. Mapping 22q11.2 gene dosage effects on brain morphometry[J]. J Neu-rosci, 2017, 37(26):6183-6199.
[23] Voll SL, Boot E, Butcher NJ, et al. Obesity in adults with 22q11.2 deletion syndrome[J]. Genet Med, 2017, 19(2):204-208.
[24] Trainor PA, Andrews BT. Facial dysostoses: etiology, pathogenesis and management[J]. Am J Med Genet C Semin Med Genet, 2013, 163C(4):283-294.
[25] Terrazas K, Dixon J, Trainor PA , et al. Rare syndro-mes of the head and face: mandibulofacial and acrofacial dysostoses[J]. Wiley Interdiscip Rev Dev Biol, 2017, 6(3): 10.1002/wdev.263.
[26] Dauwerse JG, Dixon J, Seland S, et al. Mutations in genes encoding subunits of RNA polymerasesⅠandⅢcause Treacher Collins syndrome[J]. Nat Genet, 2011, 43(1):20-22.
doi: 10.1038/ng.724
[27] Schaefer E, Collet C, Genevieve D, et al. Autosomal recessive POLR1D mutation with decrease of TC-OF1 mRNA is responsible for Treacher Collins syndrome[J]. Genet Med, 2014, 16(9):720-724.
doi: 10.1038/gim.2014.12 pmid: 24603435
[28] Noack Watt KE, Achilleos A, Neben CL, et al. The roles of RNA polymeraseⅠandⅢsubunits Polr1c and Polr1d in craniofacial development and in zebrafish models of treacher collins syndrome[J]. PLoS Genet, 2016, 12(7):e1006187.
[29] Ross AP, Zarbalis KS. The emerging roles of ribosome biogenesis in craniofacial development[J]. Front Physiol, 2014, 5:26.
[30] Sakai D, Dixon J, Dixon MJ, et al. Mammalian neurogenesis requires Treacle-Plk1 for precise control of spindle orientation, mitotic progression, and main-tenance of neural progenitor cells[J]. PLoS Genet, 2012, 8(3):e1002566.
[31] de Peralta MS, Mouguelar VS, Sdrigotti MA, et al. Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes[J]. Cell Death Dis, 2016, 7(10):e2397.
[32] Kwong EML, Ho JCH, Lau MCC, et al. Restoration of polr1c in early embryogenesis rescues the type 3 treacher collins syndrome facial malformation phenotype in zebrafish[J]. Am J Pathol, 2018, 188(2):336-342.
doi: 10.1016/j.ajpath.2017.10.004
[33] Wilkie AO, Slaney SF, Oldridge M, et al. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome[J]. Nat Genet, 1995, 9(2):165-172.
pmid: 7719344
[34] Goriely A, Wilkie AO. Paternal age effect mutations and selfish spermatogonial selection: causes and con-sequences for human disease[J]. Am J Hum Genet, 2012, 90(2):175-200.
doi: 10.1016/j.ajhg.2011.12.017 pmid: 22325359
[35] Arnheim N, Calabrese P. Germline stem cell competition, mutation hot spots, genetic disorders, and ol-der fathers[J]. Annu Rev Genomics Hum Genet, 2016, 17:219-243.
doi: 10.1146/annurev-genom-083115-022656 pmid: 27070266
[36] Ferreira LC, Dantas Junior JH. Report of a father with congenital bBilateral absence of the vas defe-rens fathering a child with Beare-Stevenson syndrome[J]. Front Genet, 2020, 11:104.
doi: 10.3389/fgene.2020.00104
[37] Maher GJ, Ralph HK, Ding ZH, et al. Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes[J]. Genome Res, 2018, 28(12):1779-1790.
doi: 10.1101/gr.239186.118
[38] Martin LA, Assif N, Gilbert M, et al. Enhanced fitness of adult spermatogonial stem cells bearing a paternal age-associated FGFR2 mutation[J]. Stem Cell Reports, 2014, 3(2):219-226.
doi: 10.1016/j.stemcr.2014.06.007 pmid: 25254335
[39] Yoon SR, Choi SK, Eboreime J, et al. Age-dependent germline mosaicism of the most common noo-nan syndrome mutation shows the signature of germ-line selection[J]. Am J Hum Genet, 2013, 92(6):917-926.
doi: 10.1016/j.ajhg.2013.05.001
[40] Park WJ, Theda C, Maestri NE, et al. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome[J]. Am J Hum Genet, 1995, 57(2):321-328.
pmid: 7668257
[41] Chen P, Zhang L, Weng TJ, et al. A Ser252Trp mutation in fibroblast growth factor receptor 2 (FGFR2) mimicking human Apert syndrome reveals an essential role for FGF signaling in the regulation of endochondral bone formation[J]. PLoS One, 2014, 9(1):e87311.
[42] Xu W, Luo FT, Wang Q, et al. Inducible activation of FGFR2 in adult mice promotes bone formation after bone marrow ablation[J]. J Bone Miner Res, 2017, 32(11):2194-2206.
doi: 10.1002/jbmr.3204
[43] Suzuki H, Suda N, Shiga M, et al. Apert syndrome mutant FGFR2 and its soluble form reciprocally alter osteogenesis of primary calvarial osteoblasts[J]. J Cell Physiol, 2012, 227(9):3267-3277.
doi: 10.1002/jcp.24021
[44] Min Swe NM, Kobayashi Y, Kamimoto H, et al. A-berrantly activated Wnt/β-catenin pathway co-receptors LRP5 and LRP6 regulate osteoblast differentiation in the developing coronal sutures of an Apert syndrome (Fgfr2S252W/+) mouse model[J]. Dev Dyn, 2021, 250(3):465-476.
doi: 10.1002/dvdy.v250.3
[45] Azoury SC, Reddy S, Shukla V, et al. Fibroblast growth factor receptor 2 (FGFR2) mutation related syndromic craniosynostosis[J]. Int J Biol Sci, 2017, 13(12):1479-1488.
doi: 10.7150/ijbs.22373 pmid: 29230096
[46] Carter EP, Fearon AE, Grose RP. Careless talk costs lives: fibroblast growth factor receptor signalling and the consequences of pathway malfunction[J]. Trends Cell Biol, 2015, 25(4):221-233.
doi: 10.1016/j.tcb.2014.11.003
[47] Morita J, Nakamura M, Kobayashi Y, et al. Soluble form of FGFR2 with S252W partially prevents craniosynostosis of the apert mouse model[J]. Dev Dyn, 2014, 243(4):560-567.
doi: 10.1002/dvdy.v243.4
[48] Wang Y, Zhou X, Oberoi K, et al. p38 Inhibition ameliorates skin and skull abnormalities in Fgfr2 Bea-re-Stevenson mice[J]. J Clin Invest, 2012, 122(6):2153-2164.
doi: 10.1172/JCI62644
[49] Yokota M, Kobayashi Y, Morita J, et al. Therapeutic effect of nanogel-based delivery of soluble FGFR2 with S252W mutation on craniosynostosis[J]. PLoS One, 2014, 9(7):e101693.
doi: 10.1371/journal.pone.0101693
[50] Kim B, Shin H, Kim W, et al. PIN1 attenuation improves midface hypoplasia in a mouse model of a-pert syndrome[J]. J Dent Res, 2020, 99(2):223-232.
doi: 10.1177/0022034519893656 pmid: 31869252
[51] Wójcicki P, Koźlik MJ, Wójcicka K. Genetic factors in selected complex congenital malformations with cleft defect[J]. Adv Clin Exp Med, 2016, 25(5):977-987.
doi: 10.17219/acem/61911 pmid: 28028964
[52] Marwaha M, Nanda KD. Ectrodactyly, ectodermal dysplasia, cleft lip, and palate (EEC syndrome)[J]. Contemp Clin Dent, 2012, 3(2):205-208.
doi: 10.4103/0976-237X.96831
[53] Shivaprakash PK, Joshi HV, Noorani H, et al. Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome: a case report of “Incomplete syndrome”[J]. Contemp Clin Dent, 2012, 3(Suppl 1):S115-S117.
[54] Barbaro V, Confalonieri L, Vallini I, et al. Development of an allele-specific real-time PCR assay for discrimination and quantification of p63 R279H mutation in EEC syndrome[J]. J Mol Diagn, 2012, 14(1):38-45.
doi: 10.1016/j.jmoldx.2011.07.008
[55] Qu JQ, Tanis SEJ, Smits JPH, et al. Mutant p63 affects epidermal cell identity through rewiring the enhancer landscape[J]. Cell Rep, 2018, 25(12): 3490-3503.e4.
doi: 10.1016/j.celrep.2018.11.039
[56] Qu JQ, Yi GQ, Zhou HQ. P63 cooperates with CT-CF to modulate chromatin architecture in skin keratinocytes[J]. Epigenetics Chromatin, 2019, 12(1):31.
doi: 10.1186/s13072-019-0280-y
[57] Shen JF, van den Bogaard EH, Kouwenhoven EN, et al. APR-246/Prima-1(MET) rescues epidermal differentiation in skin keratinocytes derived from EEC syndrome patients with p63 mutations[J]. Proc Natl Acad Sci U S A, 2013, 110(6):2157-2162.
doi: 10.1073/pnas.1201993110
[58] Novelli F, Lena AM, Panatta E, et al. Allele-specific silencing of EEC p63 mutant R304W restores p63 transcriptional activity[J]. Cell Death Dis, 2016, 7:e2227.
[59] Barbaro V, Nasti AA, Del Vecchio C, et al. Correction of mutant p63 in EEC syndrome using siRNA mediated allele-specific silencing restores defective stem cell function[J]. Stem Cells, 2016, 34(6):1588-1600.
doi: 10.1002/stem.v34.6
[60] de Lima RL, Hoper SA, Ghassibe M, et al. Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome[J]. Genet Med, 2009, 11(4):241-247.
doi: 10.1097/GIM.0b013e318197a49a
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