PDF(Pubmed)
Abstract：
UNASSIGNED: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.
UNASSIGNED: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.
UNASSIGNED: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.
UNASSIGNED: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.
UNASSIGNED: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.
UNASSIGNED: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.
UNASSIGNED: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.
摘要：
■少汗症外胚层发育不良（HED）是一种影响外胚层起源结构的遗传性疾病，比如牙齿,头发,和汗腺。与常染色体隐性和显性遗传方式相比，X-连锁HED（XLHED）的特点是缺牙症/少牙症，没有/稀疏的头发，多汗症/多汗症，和特征性的面部特征，是最常见的，其主要原因是外生体异常蛋白A（EDA）基因的突变。本研究旨在阐述中国男性XLHED的临床和分子特征，并总结和比较先前的一些发现。
■基因组DNA是从先证者及其家庭成员的外周血中获得的，然后使用Sanger测序进行EDA的突变分析。采用实时定量PCR和Western印迹法检测EDA的表达。使用荧光素酶测定法检测NF-κB的转录活性。
■具有XLHED的先证者被鉴定为新的EDA突变，c.1119G>C（p。M373I),影响了跨膜蛋白外显子8突变的分子分析，继承自母亲。他表现出严重的多颗牙齿脱落，缺少20多颗恒牙，头发和眉毛稀疏，干,薄,皮肤瘙痒。此外，他的出汗功能在一定程度上是异常的。
■功能研究表明，这种新型突变体导致NF-κB的EDA表达水平和转录活性显着降低。我们的发现扩展了XLHED患者中EDA突变的范围，为进一步探讨XLHED的发病机制提供了依据和思路。
■基因组DNA是从先证者及其家庭成员的外周血中获得的，然后使用Sanger测序进行EDA的突变分析。采用实时定量PCR和Western印迹法检测EDA的表达。使用荧光素酶测定法检测NF-κB的转录活性。
■具有XLHED的先证者被鉴定为新的EDA突变，c.1119G>C（p。M373I),影响了跨膜蛋白外显子8突变的分子分析，继承自母亲。他表现出严重的多颗牙齿脱落，缺少20多颗恒牙，头发和眉毛稀疏，干,薄,皮肤瘙痒。此外，他的出汗功能在一定程度上是异常的。
■功能研究表明，这种新型突变体导致NF-κB的EDA表达水平和转录活性显着降低。我们的发现扩展了XLHED患者中EDA突变的范围，为进一步探讨XLHED的发病机制提供了依据和思路。
