少汗型外胚叶发育不良中EDA基因新突变位点的鉴定

doi:10.19438/j.cjoms.2021.05.008

中国口腔颌面外科杂志 ›› 2021, Vol. 19 ›› Issue (5): 429-433.doi: 10.19438/j.cjoms.2021.05.008

少汗型外胚叶发育不良中EDA基因新突变位点的鉴定

喻康¹, 沈意涵¹, 蒋彩玲¹, 王凤², 吴轶群¹

1.上海交通大学医学院附属第九人民医院口腔第二门诊部;
2.口腔种植科,上海交通大学口腔医学院, 国家口腔医学中心,国家口腔疾病临床医学研究中心,上海市口腔医学重点实验室,上海 200011

收稿日期:2021-01-18 修回日期:2021-03-09 出版日期:2021-09-20 发布日期:2021-10-20
通讯作者: 吴轶群,E-mail：yiqunwu@hotmail.com
作者简介:喻康（1995-）,男,硕士研究生,E-mail：kqyukang@163.com
基金资助:
国家自然科学基金（81700944）; 上海交通大学医工（理）交叉基金（YG2016ZD01）

A novel EDA gene mutation identified by whole exome sequencing in one patient with HED

YU Kang¹, SHEN Yi-han¹, JIANG Cai-ling¹, WANG Feng², WU Yi-qun¹

1. Department of Second Dental Center;
2. Department of Oral Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology. Shanghai 200011, China

Received:2021-01-18 Revised:2021-03-09 Online:2021-09-20 Published:2021-10-20

摘要/Abstract

摘要： 目的揭示少汗型外胚叶发育不良（hypohidrotic ectodermal dysplasia,HED）一种新的外异蛋白A（ectodysplasin A,EDA）基因突变。方法抽取患者外周血,提取基因组DNA,运用全外显子测序方法对患者进行基因测序,使用一代Sanger测序验证突变位点。构建EDA1（ectodysplasin A1）野生型及突变型表达质粒,通过蛋白免疫印迹法检测EDA1突变型蛋白的表达和分泌;通过双荧光素酶分析,检测EDA1突变型蛋白对下游NF-κB通路活性的影响。采用SPSS 20.0 软件包对数据进行t检验。结果发现了1例未报道的EDA基因突变位点c.649_666del （p.Pro217_Pro222del）。与野生型EDA1相比,突变型EDA1蛋白能正常表达和分泌,但其对下游NF-κB的转录激活显著降低（P<0.05）。结论本研究鉴定了1例新的EDA基因缺失突变,扩展了X连锁少汗型外胚叶发育不良的突变谱,有助于产前咨询、诊断和矫正。

关键词: 少汗型外胚叶发育不良, EDA, 全外显子测序, 基因突变

Abstract: PURPOSE: This study aimed at revealing a novel ectodysplasin A (EDA) gene mutation in one hypohidrotic ectodermal dysplasia (HED) family. METHODS: Genomic DNA was extracted from peripheral blood of patients, and whole exome sequencing was used for gene sequencing. EDA1 (ectodysplasin A1) wild-type and mutant expression plasmids were constructed. Protein expression levels were detected by Western blotting. The effect on downstream NF-κB pathway activity was detected by dual luciferase analysis. The data was analyzed with SPSS 20.0 software. RESULTS: We identified a novel EDA c.649_666del (p.Pro217_Pro222del) mutation. Compared with wild-type EDA1, the mutant EDA1 protein can be expressed and secreted normally, but its transcriptional activation of downstream NF-κB pathway was significantly decreased(P<0.05). CONCLUSIONS: This study identified a novel deletion mutation of EDA gene, which expanded the mutation spectrum of X-linked hypohidrotic ectodermal dysplasia and can be helpful for prenatal consultation, diagnosis and correction.

Key words: Hypohidrotic ectodermal dysplasia, EDA, Whole exome sequencing, Gene mutation

中图分类号:

R783.4

喻康, 沈意涵, 蒋彩玲, 王凤, 吴轶群. 少汗型外胚叶发育不良中EDA基因新突变位点的鉴定[J]. 中国口腔颌面外科杂志, 2021, 19(5): 429-433.

YU Kang, SHEN Yi-han, JIANG Cai-ling, WANG Feng, WU Yi-qun. A novel EDA gene mutation identified by whole exome sequencing in one patient with HED[J]. China J Oral Maxillofac Surg, 2021, 19(5): 429-433.

参考文献

[1] Wright JT, Fete M, Schneider H, et al.Ectodermal dysplasias: classification and organization by phenotype, genotype and molecular pathway[J]. Am J Med Genet A, 2019, 179(3): 442-447.
[2] Nguyen-Nielsen M, Skovbo S, Svaneby D, et al.The prevalence of X-linked hypohidrotic ectodermal dysplasia (XLHED) in Denmark, 1995-2010[J]. Eur J Med Genet, 2013, 56(5): 236-242.
[3] Anbouba GM, Carmany EP, Natoli JL.The characterization of hypodontia, hypohidrosis, and hypotrichosis associated with X-linked hypohidrotic ectodermal dysplasia: a systematic review[J]. Am J Med Genet A, 2020, 182(4): 831-841.
[4] Blüschke G, Nüsken KD, Schneider H.Prevalence and prevention of severe complications of hypohidrotic ectodermal dysplasia in infancy[J]. Early Hum Dev, 2010, 86(7): 397-399.
[5] Mikkola ML.Molecular aspects of hypohidrotic ectodermal dysplasia[J]. Am J Med Genet A, 2009, 149A(9): 2031-2036.
[6] Guazzarotti L, Tadini G, Mancini G, et al.WNT10A gene is the second molecular candidate in a cohort of young Italian subjects with ectodermal derivative impairment[J]. Clin Genet, 2018, 93(3): 693-698.
[7] Sadier A, Viriot L, Pantalacci S, et al.The ectodysplasin pathway: from diseases to adaptations[J]. Trends Genet, 2014, 30(1): 24-31.
[8] Kowalczyk-Quintas C, Schneider P. Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation[J]. Cytokine Growth Factor Rev, 2014, 25(2): 195-203.
[9] Trzeciak WH, Koczorowski R.Molecular basis of hypohidrotic ectodermal dysplasia: an update[J]. J Appl Genet, 2016, 57(1): 51-61.
[10] Lin Y, Yin W, Bian Z.Mutation detection and prenatal diagnosis of XLHED pedigree[J]. PeerJ, 2017, 5: e3691.
[11] Hammersen J, Wohlfart S, Goecke TW, et al.Reliability of prenatal detection of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography[J]. Prenat Diagn, 2019, 39(9): 796-805.
[12] Reyes-Reali J, Mendoza-Ramos M, Garrido-Guerrero E, et al.Hypohidrotic ectodermal dysplasia: clinical and molecular review[J]. Int J Dermatol, 2018, 57(8): 965-972.
[13] Schneider P, Street S, Gaide O, et al.Mutations leading to X-linked hypohidrotic ectodermal dysplasia affect three major functional domains in the tumor necrosis factor family member ectodysplasin-A[J]. J Biol Chem, 2001, 276(22): 18819-18827.
[14] Wang X, Zhang Z, Yuan S, et al.A novel EDA1 missense mutation in X-linked hypohidrotic ectodermal dysplasia[J]. Medicine (Baltimore), 2020, 99(11): e19244.
[15] Liu G, Wang X, Qin M, et al.A novel missense mutation p.S305R of EDA gene causes XLHED in a Chinese family[J]. Arch Oral Biol, 2019, 107: 104507.
[16] Chen Y, Molloy SS, Thomas L, et al.Mutations within a furin consensus sequence block proteolytic release of ectodysplasin-A and cause X-linked hypohidrotic ectodermal dysplasia[J]. Proc Natl Acad Sci USA, 2001, 98(13): 7218-7223.
[17] Swee LK, Ingold-Salamin K, Tardivel A, et al.Biological activity of ectodysplasin A is conditioned by its collagen and heparan sulfate proteoglycan-binding domains[J]. J Biol Chem, 2009, 284(40): 27567-27576.
[18] Bildik T, Ozbaran B, Kose S, et al.Hypohidrotic ectodermal dysplasia: a multidisciplinary approach[J]. Int J Psychiatry Med, 2012, 44(3): 225-240.
[19] Schnabl D, Grunert I, Schmuth M, et al.Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: a systematic review[J]. J Oral Rehabil, 2018, 45(7): 555-570.
[20] Schneider H, Faschingbauer F, Schuepbach-Mallepell S, et al.Prenatal correction of X-linked hypohidrotic ectodermal dysplasia[J]. N Engl J Med, 2018, 378(17): 1604-1610.

少汗型外胚叶发育不良中EDA基因新突变位点的鉴定

A novel EDA gene mutation identified by whole exome sequencing in one patient with HED

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