Zeng Binghui, Xiao Xue, Li Sijie, Lu Hui, Lu Jiaxuan, Zhu Ling, Yu Dongsheng, Zhao Wei
Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
Genes (Basel). 2016 Sep 19;7(9):65. doi: 10.3390/genes7090065.
Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the teeth, hair, and sweat glands. Ectodysplasin A (EDA), Ectodysplasin A receptor (EDAR), and EDAR-associated death domain (EDARADD) are candidate genes for HED, but the relationship between WNT10A and HED has not yet been validated. In this study, we included patients who presented at least two of the three ectodermal dysplasia features. The four genes were analyzed in seven HED patients by PCR and Sanger sequencing. Five EDA and one EDAR heterozygous mutations were identified in families 1-6. Two WNT10A heterozygous mutations were identified in family 7 as a compound heterozygote. c.662G>A (p.Gly221Asp) in EDA and c.354T>G (p.Tyr118*) in WNT10A are novel mutations. Bioinformatics analyses results confirmed the pathogenicity of the two novel mutations. In family 7, we also identified two single-nucleotide polymorphisms (SNPs) that were predicted to affect the splicing of EDAR. Analysis of the patient's total RNA revealed normal splicing of EDAR. This ascertained that the compound heterozygous WNT10A mutations are the genetic defects that led to the onset of HED. Our data revealed the genetic basis of seven HED patients and expended the mutational spectrum. Interestingly, we confirmed WNT10A as a candidate gene of HED and we propose WNT10A to be tested in EDA-negative HED patients.
少汗型外胚层发育不良（HED）的特征是牙齿、毛发和汗腺发育异常。外胚层发育不良蛋白A（EDA）、外胚层发育不良蛋白A受体（EDAR）和EDAR相关死亡结构域（EDARADD）是HED的候选基因，但WNT10A与HED之间的关系尚未得到证实。在本研究中，我们纳入了出现至少两种外胚层发育不良特征的患者。通过PCR和桑格测序对7例HED患者的这四个基因进行了分析。在1 - 6家族中鉴定出5个EDA杂合突变和1个EDAR杂合突变。在7家族中鉴定出2个WNT10A杂合突变，为复合杂合子。EDA中的c.662G>A（p.Gly221Asp）和WNT10A中的c.354T>G（p.Tyr118*）是新的突变。生物信息学分析结果证实了这两个新突变的致病性。在7家族中，我们还鉴定出两个预测会影响EDAR剪接的单核苷酸多态性（SNP）。对患者总RNA的分析显示EDAR剪接正常。这确定了复合杂合的WNT10A突变是导致HED发病的遗传缺陷。我们的数据揭示了7例HED患者的遗传基础并扩展了突变谱。有趣的是，我们证实WNT10A是HED的候选基因，并建议在EDA阴性的HED患者中对WNT10A进行检测。
