Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern
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 pred...
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MDPI AG
2022-09-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/12/10/2300 |
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| author | Haochen Liu Lanxin Su Hangbo Liu Jinglei Zheng Hailan Feng Yang Liu Miao Yu Dong Han |
| author_facet | Haochen Liu Lanxin Su Hangbo Liu Jinglei Zheng Hailan Feng Yang Liu Miao Yu Dong Han |
| author_sort | Haochen Liu |
| collection | DOAJ |
| description | 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 <i>androgen receptor</i> (<i>AR</i>) gene in peripheral blood cells. Two novel <i>Ectodysplasin-A</i> (<i>EDA</i>) 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 <i>EDA</i> and the phenotype spectrum of XLHED, which could help with clinical diagnosis, treatment, and genetic counseling. |
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| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T20:23:51Z |
| publishDate | 2022-09-01 |
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| series | Diagnostics |
| spelling | doaj.art-fa9d2c5bcbde4565868acdadfa80f07e2023-11-23T23:42:54ZengMDPI AGDiagnostics2075-44182022-09-011210230010.3390/diagnostics12102300Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation PatternHaochen Liu0Lanxin Su1Hangbo Liu2Jinglei Zheng3Hailan Feng4Yang Liu5Miao Yu6Dong Han7Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaDepartment of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, ChinaThe 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 <i>androgen receptor</i> (<i>AR</i>) gene in peripheral blood cells. Two novel <i>Ectodysplasin-A</i> (<i>EDA</i>) 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 <i>EDA</i> and the phenotype spectrum of XLHED, which could help with clinical diagnosis, treatment, and genetic counseling.https://www.mdpi.com/2075-4418/12/10/2300<i>Ectodysplasin-A</i> (<i>EDA</i>)skewed X-chromosome inactivationX-linked hypohidrotic ectodermal dysplasia (XLHED)phenotypic analysis |
| spellingShingle | Haochen Liu Lanxin Su Hangbo Liu Jinglei Zheng Hailan Feng Yang Liu Miao Yu Dong Han Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern Diagnostics <i>Ectodysplasin-A</i> (<i>EDA</i>) skewed X-chromosome inactivation X-linked hypohidrotic ectodermal dysplasia (XLHED) phenotypic analysis |
| title | Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern |
| title_full | Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern |
| title_fullStr | Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern |
| title_full_unstemmed | Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern |
| title_short | Rare X-Linked Hypohidrotic Ectodermal Dysplasia in Females Associated with <i>Ectodysplasin-A</i> Variants and the X-Chromosome Inactivation Pattern |
| title_sort | rare x linked hypohidrotic ectodermal dysplasia in females associated with i ectodysplasin a i variants and the x chromosome inactivation pattern |
| topic | <i>Ectodysplasin-A</i> (<i>EDA</i>) skewed X-chromosome inactivation X-linked hypohidrotic ectodermal dysplasia (XLHED) phenotypic analysis |
| url | https://www.mdpi.com/2075-4418/12/10/2300 |
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