Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics
Background: Ectodysplasin A (EDA) variations are major pathogenic factors for hypohidrotic ectodermal dysplasia (HED), the most common form of ectodermal dysplasia (ED), characterized by hypotrichosis, hypohidrosis, hypodontia, and other oral features.Methods: Molecular genetic defects in three HED...
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.916340/full |
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| author | Yupei Wang Yupei Wang Chuan Zhang Chuan Zhang Bingbo Zhou Bingbo Zhou Ling Hui Ling Hui Lei Zheng Lei Zheng Xue Chen Xue Chen Shifan Wang Shifan Wang Lan Yang Lan Yang Shengju Hao Shengju Hao Qinghua Zhang Qinghua Zhang |
| author_facet | Yupei Wang Yupei Wang Chuan Zhang Chuan Zhang Bingbo Zhou Bingbo Zhou Ling Hui Ling Hui Lei Zheng Lei Zheng Xue Chen Xue Chen Shifan Wang Shifan Wang Lan Yang Lan Yang Shengju Hao Shengju Hao Qinghua Zhang Qinghua Zhang |
| author_sort | Yupei Wang |
| collection | DOAJ |
| description | Background: Ectodysplasin A (EDA) variations are major pathogenic factors for hypohidrotic ectodermal dysplasia (HED), the most common form of ectodermal dysplasia (ED), characterized by hypotrichosis, hypohidrosis, hypodontia, and other oral features.Methods: Molecular genetic defects in three HED families were detected by whole-exome sequencing and confirmed by Sanger sequencing or multiplex ligation-dependent probe amplification. The effect of splicing variant was further verified by EDA minigene in vitro analysis. De novo deletion was confirmed by chromosomal microarray analysis.Results: Three variants (c.396 + 1 G > C, c.171-173 del GTT, and exon 1 deletion) were identified, all affecting exon 1 of the EDA gene. Variants c.396 + 1 G > C and c.171-173 del GTT were first identified. Minigene analysis of the splicing variant (c.396 + 1 G > C) displayed a prolonged EDA-A1 transcript containing extra 699 bp at the start of intron 1, representing a functional cryptic splice site formation in vitro. Combining the results of chromosomal microarray analysis and whole-exome sequencing, the deletion variant was over 87 kb. Three variants were predicted to affect protein function to differing degrees, and were responsible for X-linked HED with varying phenotype.Conclusion: Investigating the clinical and molecular characteristics of these variations broadens our understanding of EDA gene variants, supporting clinical diagnosis, genetic counseling, and prenatal diagnosis of HED. |
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| language | English |
| last_indexed | 2024-04-13T11:45:51Z |
| publishDate | 2022-07-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-5211740d0e82493f9f9a8cdb20637ccd2022-12-22T02:48:10ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-07-011310.3389/fgene.2022.916340916340Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular CharacteristicsYupei Wang0Yupei Wang1Chuan Zhang2Chuan Zhang3Bingbo Zhou4Bingbo Zhou5Ling Hui6Ling Hui7Lei Zheng8Lei Zheng9Xue Chen10Xue Chen11Shifan Wang12Shifan Wang13Lan Yang14Lan Yang15Shengju Hao16Shengju Hao17Qinghua Zhang18Qinghua Zhang19Medical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaMedical Genetics Center, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, ChinaGansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Lanzhou, ChinaBackground: Ectodysplasin A (EDA) variations are major pathogenic factors for hypohidrotic ectodermal dysplasia (HED), the most common form of ectodermal dysplasia (ED), characterized by hypotrichosis, hypohidrosis, hypodontia, and other oral features.Methods: Molecular genetic defects in three HED families were detected by whole-exome sequencing and confirmed by Sanger sequencing or multiplex ligation-dependent probe amplification. The effect of splicing variant was further verified by EDA minigene in vitro analysis. De novo deletion was confirmed by chromosomal microarray analysis.Results: Three variants (c.396 + 1 G > C, c.171-173 del GTT, and exon 1 deletion) were identified, all affecting exon 1 of the EDA gene. Variants c.396 + 1 G > C and c.171-173 del GTT were first identified. Minigene analysis of the splicing variant (c.396 + 1 G > C) displayed a prolonged EDA-A1 transcript containing extra 699 bp at the start of intron 1, representing a functional cryptic splice site formation in vitro. Combining the results of chromosomal microarray analysis and whole-exome sequencing, the deletion variant was over 87 kb. Three variants were predicted to affect protein function to differing degrees, and were responsible for X-linked HED with varying phenotype.Conclusion: Investigating the clinical and molecular characteristics of these variations broadens our understanding of EDA gene variants, supporting clinical diagnosis, genetic counseling, and prenatal diagnosis of HED.https://www.frontiersin.org/articles/10.3389/fgene.2022.916340/fullhypohidrotic ectodermal dysplasiaEDAwhole-exome sequencingsplicing variantcryptic splice siteHED |
| spellingShingle | Yupei Wang Yupei Wang Chuan Zhang Chuan Zhang Bingbo Zhou Bingbo Zhou Ling Hui Ling Hui Lei Zheng Lei Zheng Xue Chen Xue Chen Shifan Wang Shifan Wang Lan Yang Lan Yang Shengju Hao Shengju Hao Qinghua Zhang Qinghua Zhang Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics Frontiers in Genetics hypohidrotic ectodermal dysplasia EDA whole-exome sequencing splicing variant cryptic splice site HED |
| title | Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics |
| title_full | Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics |
| title_fullStr | Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics |
| title_full_unstemmed | Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics |
| title_short | Three Variants Affecting Exon 1 of Ectodysplasin A Cause X-Linked Hypohidrotic Ectodermal Dysplasia: Clinical and Molecular Characteristics |
| title_sort | three variants affecting exon 1 of ectodysplasin a cause x linked hypohidrotic ectodermal dysplasia clinical and molecular characteristics |
| topic | hypohidrotic ectodermal dysplasia EDA whole-exome sequencing splicing variant cryptic splice site HED |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.916340/full |
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