Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with Ectodysplasin-A Variants and the X-Chromosome Inactivation Pattern.
Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with Ectodysplasin-A Variants and the X-Chromosome Inactivation Pattern.
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DOI：
10.3390/diagnostics12102300
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发表时间：
2022-09-23
期刊：
影响因子：
3.6
通讯作者：
Han, Dong
中科院分区：
文献类型：
--
作者：
Liu, Haochen;Su, Lanxin;Liu, Hangbo;Zheng, Jinglei;Feng, Hailan;Liu, Yang;Yu, Miao;Han, Dong
关键词：
本研究的目的是确定致病基因变异的女性患者与严重的X连锁少汗性外胚层发育不良（XLHED）。采用全外显子组测序（WES）和桑格测序（Sanger sequencing）方法筛选致病基因变异。通过生物信息学预测了这些变异的危害性。然后，通过PCR分析外周血细胞中人雄激素受体（AR）基因CAG重复区，测量偏斜X染色体失活（XCI）。在3例女性XLHED患者中鉴定出2种新的外胚层发育异常-A（EDA）杂合变体（c.588_606del19bp和c.837G>A）和1种杂合变体（c.1045G>A，rs 132630317）。生物信息学分析表明这些变异可能具有致病性。三级结构分析表明，这些变异体可导致EDA蛋白的结构损伤。偏斜X染色体失活的分析显示，在患者#35中发现了极端偏斜X染色体失活（98：2），而在患者#347和#204中相对中度（21：79和30：70）。本研究拓宽了EDA的变异谱和XLHED的表型谱，为临床诊断、治疗和遗传咨询提供了依据。
The goal of this study was to identify the pathogenic gene variants in female patients with severe X-linked hypohidrotic ectodermal dysplasia (XLHED). Whole-exome sequencing (WES) and Sanger sequencing were used to screen for the pathogenic gene variants. The harmfulness of these variations was predicted by bioinformatics. Then, skewed X-chromosome inactivation (XCI) was measured by PCR analysis of the CAG repeat region in the human androgen receptor (AR) gene in peripheral blood cells. Two novel Ectodysplasin-A (EDA) heterozygous variants (c.588_606del19bp and c.837G>A) and one heterozygous variant (c.1045G>A, rs132630317) were identified in the three female XLHED patients. The bioinformatics analysis showed that these variants might be pathogenic. The tertiary structure analysis showed that these variants could cause structural damage to EDA proteins. Analysis of the skewed X-chromosome inactivation revealed that extreme skewed X-chromosome inactivation was found in patient #35 (98:2), whereas it was comparatively moderate in patients #347 and #204 (21:79 and 30:70). Our results broaden the variation spectrum of EDA and the phenotype spectrum of XLHED, which could help with clinical diagnosis, treatment, and genetic counseling.
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影响因子：
1.9
作者：
Han, Dong;Gong, Yu;Song, Shujuan
通讯作者：
Song, Shujuan
DOI：
10.1016/j.xhgg.2022.100121
发表时间：
2022-07-14
期刊：
HUMAN GENETICS AND GENOMICS ADVANCES
影响因子：
--
作者：
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通讯作者：
Wilson, Melissa A.
影响因子：
2
作者：
Burger, Kristin;Schneider, Anne-Theres;Schneider, Holm
通讯作者：
Schneider, Holm
影响因子：
3.7
作者：
Carmen Martinez-Romero, Maria;Juliana Ballesta-Martinez, Maria;Jose Trujillo-Tiebas, Ma
通讯作者：
Jose Trujillo-Tiebas, Ma
DOI：
10.1089/gte.2008.0020
发表时间：
2008-09-01
期刊：
GENETIC TESTING
影响因子：
--
作者：
Conte, Chiara;Gambardella, Stefano;Novelli, Giuseppe
通讯作者：
Novelli, Giuseppe