■分析1例少汗症外胚层发育不良(HED)患者的致病基因,探讨致病基因与寡头表型的关系。
■从患有HED的患者收集临床数据和外周血。通过全外显子测序(WES)分析致病基因,并通过Singer测序进行验证。预测变体蛋白的二级和三级结构以分析它们的毒性。
■患者表现出严重的寡头畸形表型,其中上颚只剩下两个落叶犬。WES揭示了半合子EDA变体c.466C>Tp。(Arg156Cys)和新的杂合EVC2变体c.1772T>Cp。(Leu591Ser)。EDA变体p.(Arg156Cys)和EVC2变体p.(Leu591Ser)的二级和三级结构的预测表明两种分子的功能受损。
■与由EDA变体c.466C>T引起的其他患者相比,该患者表现出更严重的寡头畸形表型。由于Evc2是SonicHedgehog(Shh)信号通路的正调节因子,我们推测EVC2变异体p.(Leu591Ser)可能在HED的寡头表型中发挥协同作用,从而加剧了寡头表型。了解由多个基因变异引起的寡头畸形对于理解寡头畸形表型的个体差异具有重要意义。
UNASSIGNED: To analyse the pathogenic genes in a patient with hypohidrotic ectodermal dysplasia (HED) and explore the relationship between pathogenic genes and the oligodontia phenotype.
UNASSIGNED: Clinical data and peripheral blood were collected from a patient with HED. Pathogenic genes were analysed by whole-exon sequencing (WES) and verified by Singer sequencing. The secondary and tertiary structures of the variant proteins were predicted to analyse their toxicity.
UNASSIGNED: The patient exhibited a severe oligodontia phenotype, wherein only two deciduous canines were left in the upper jaw. WES revealed a hemizygous EDA variant c.466C > T p.(Arg156Cys) and a novel heterozygous
EVC2 variant c.1772T > C p.(Leu591Ser). Prediction of the secondary and tertiary structures of the EDA variant p.(Arg156Cys) and
EVC2 variant p.(Leu591Ser) indicated impaired function of both molecules.
UNASSIGNED: The patient demonstrated a more severe oligodontia phenotype when compared with the other patients caused by the EDA variant c.466C > T. Since
Evc2 is a positive regulator of the Sonic Hedgehog (Shh) signal pathway, we speculated that the
EVC2 variant p.(Leu591Ser) may play a synergistic role in the oligodontia phenotype of HED, thereby exacerbating the oligodontia phenotype. Knowledge of oligodontia caused by multiple gene variants is of great significance for understanding individual differences in oligodontia phenotypes.