少汗性外胚层发育不良患者EDA基因突变检测及表型分析Detection of EDA gene mutation and phenotypic analysis in patients with hypohidrotic ectodermal dysplasia
吴君怡;余淼;孙仕晨;樊壮壮;郑静蕾;张刘陶;冯海兰;刘洋;韩冬;
摘要(Abstract)：
目的:在少汗性外胚层发育不良(hypohidrotic ectodermal dysplasia,HED)患者中检测ectodysplasin A(EDA基因突变,汇总并分析携带EDA基因突变的HED患者的缺失恒牙分布特点及全身临床表现。方法:对临床收集到的12个HED家系进行遗传病史采集、全身系统性检查和口内检查,通过采集先证者及其家族成员的外周静脉血或唾液样本,提取基因组DNA,聚合酶链式反应(polymerase chain reaction,PCR)扩增EDA基因编码区并进行Sanger测序,与正常人群的EDA基因序列(NM_001399.5)进行比对,筛查突变。利用突变功能预测、保守性分析、蛋白结构预测分析突变的功能影响,根据《美国医学遗传学和基因组学会遗传变异致病性分级指南》评估突变的致病性。总结EDA基因突变的HED患者的全身表型、缺失恒牙牙位,对比分析不同牙位缺失率的差异。结果:在12个HED家系中发现8个家系分别携带8个EDA基因突变:c.164T> C(p.Leu55Pro)、c.457C> T(p.Arg153Cys)、c.466C> T(p.Arg156Cys)、c.584G> A(p.Gly195Glu)、c.619delG(p.Gly207Profs~*73)、c.673C> T(p.Pro225Ser)、c.676C> T(p.Gln226~*)和c.905T> G(p.Phe302Cys),其中,c.164T> C(p.Leu55Pro)、c.619delG(p.Gly207Profs~*73)、c.673C> T(p.Pro225Ser)、c.676C> T(p.Gln226~*)和c.905T> G(p.Phe302Cys)为新检出的突变。本研究发现的EDA基因突变的HED患者均为男性,其平均缺失恒牙数目为(13.86±4.49)颗,其中上颌平均缺失恒牙数目为(13.14±5.76)颗,缺失率为73.02%,下颌平均缺失恒牙数目为(14.57±3.05)颗,缺失率为80.95%。牙列左、右侧同名牙缺失数目差异无统计学意义(P> 0.05)。上颌侧切牙、上颌第二前磨牙和下颌侧切牙缺失率高,而上颌中切牙、上颌第一磨牙和下颌第一磨牙缺失率低。结论:本研究在HED患者中检测出EDA基因致病突变,总结EDA基因突变的HED患者缺失恒牙规律,丰富了HED患者的EDA基因突变谱和表型谱,为遗传诊断和产前咨询提供了新的证据。
关键词(KeyWords)： 少汗性外胚层发育不良;先天性缺牙;EDA基因;基因突变
基金项目(Foundation): 国家自然科学基金(81970902、81600846)~~
作者(Author): 吴君怡;余淼;孙仕晨;樊壮壮;郑静蕾;张刘陶;冯海兰;刘洋;韩冬;
Email:
DOI: 10.19723/j.issn.1671-167X.2021.01.005
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