Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations
Ectodermal dysplasia (ED) is a diverse group of genetic disorders caused by congenital defects of two or more ectodermal-derived body structures, namely, hair, teeth, nails, and some glands, e.g., sweat glands. Molecular pathogenesis of ED involves mutations of genes encoding key proteins of major d...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/9/1389 |
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| author | Hoda A. Ahmed Ghada Y. El-Kamah Eman Rabie Mostafa I. Mostafa Maha R. Abouzaid Nehal F. Hassib Mennat I. Mehrez Mohamed A. Abdel-Kader Yasmine H. Mohsen Suher K. Zada Khalda S. Amr Inas S. M. Sayed |
| author_facet | Hoda A. Ahmed Ghada Y. El-Kamah Eman Rabie Mostafa I. Mostafa Maha R. Abouzaid Nehal F. Hassib Mennat I. Mehrez Mohamed A. Abdel-Kader Yasmine H. Mohsen Suher K. Zada Khalda S. Amr Inas S. M. Sayed |
| author_sort | Hoda A. Ahmed |
| collection | DOAJ |
| description | Ectodermal dysplasia (ED) is a diverse group of genetic disorders caused by congenital defects of two or more ectodermal-derived body structures, namely, hair, teeth, nails, and some glands, e.g., sweat glands. Molecular pathogenesis of ED involves mutations of genes encoding key proteins of major developmental pathways, including ectodysplasin (EDA) and wingless-type (WNT) pathways. The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. Molecular diagnosis is fundamental for disease management and emerging treatments. We used targeted next generation sequencing to study <i>EDA</i>, <i>EDAR</i>, <i>EDARADD</i>, and <i>WNT10A</i> genes in 45 Egyptian ED patients with or without hypohidrosis. We present genotype and phenotype data of 28 molecularly-characterized patients demonstrating genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability. Thirteen mutations were reported, including four novel <i>EDA</i> mutations, two novel <i>EDARADD</i>, and one novel <i>EDAR</i> mutations. Identified mutations congregated in exons encoding key functional domains. <i>EDA</i> is the most common gene contributing to 85% of the identified Egyptian ED genetic spectrum, followed by <i>EDARADD</i> (10%) and <i>EDAR</i> (5%). Our cohort represents the first and largest cohort from North Africa where more than 60% of ED patients were identified emphasizing the need for exome sequencing to explore unidentified cases. |
| first_indexed | 2024-03-10T07:38:34Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T07:38:34Z |
| publishDate | 2021-09-01 |
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| series | Genes |
| spelling | doaj.art-4c8efb6860764ef6a7e8e2733747332e2023-11-22T13:14:19ZengMDPI AGGenes2073-44252021-09-01129138910.3390/genes12091389Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel MutationsHoda A. Ahmed0Ghada Y. El-Kamah1Eman Rabie2Mostafa I. Mostafa3Maha R. Abouzaid4Nehal F. Hassib5Mennat I. Mehrez6Mohamed A. Abdel-Kader7Yasmine H. Mohsen8Suher K. Zada9Khalda S. Amr10Inas S. M. Sayed11Medical Molecular Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptClinical Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptMedical Molecular Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptBiology Department, School of Sciences and Engineering, The American University in Cairo (AUC), Cairo 11835, EgyptMedical Molecular Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptOrodental Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptEctodermal dysplasia (ED) is a diverse group of genetic disorders caused by congenital defects of two or more ectodermal-derived body structures, namely, hair, teeth, nails, and some glands, e.g., sweat glands. Molecular pathogenesis of ED involves mutations of genes encoding key proteins of major developmental pathways, including ectodysplasin (EDA) and wingless-type (WNT) pathways. The most common ED phenotype is hypohidrotic/anhidrotic ectodermal dysplasia (HED) featuring hypotrichosis, hypohidrosis/anhidrosis, and hypodontia. Molecular diagnosis is fundamental for disease management and emerging treatments. We used targeted next generation sequencing to study <i>EDA</i>, <i>EDAR</i>, <i>EDARADD</i>, and <i>WNT10A</i> genes in 45 Egyptian ED patients with or without hypohidrosis. We present genotype and phenotype data of 28 molecularly-characterized patients demonstrating genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability. Thirteen mutations were reported, including four novel <i>EDA</i> mutations, two novel <i>EDARADD</i>, and one novel <i>EDAR</i> mutations. Identified mutations congregated in exons encoding key functional domains. <i>EDA</i> is the most common gene contributing to 85% of the identified Egyptian ED genetic spectrum, followed by <i>EDARADD</i> (10%) and <i>EDAR</i> (5%). Our cohort represents the first and largest cohort from North Africa where more than 60% of ED patients were identified emphasizing the need for exome sequencing to explore unidentified cases.https://www.mdpi.com/2073-4425/12/9/1389ectodysplasin Aectodermal eysplasia<i>EDA</i><i>EDAR</i><i>EDARADD</i><i>WNT10A</i> |
| spellingShingle | Hoda A. Ahmed Ghada Y. El-Kamah Eman Rabie Mostafa I. Mostafa Maha R. Abouzaid Nehal F. Hassib Mennat I. Mehrez Mohamed A. Abdel-Kader Yasmine H. Mohsen Suher K. Zada Khalda S. Amr Inas S. M. Sayed Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations Genes ectodysplasin A ectodermal eysplasia <i>EDA</i> <i>EDAR</i> <i>EDARADD</i> <i>WNT10A</i> |
| title | Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations |
| title_full | Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations |
| title_fullStr | Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations |
| title_full_unstemmed | Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations |
| title_short | Gene Mutations of the Three Ectodysplasin Pathway Key Players (<i>EDA</i>, <i>EDAR</i>, and <i>EDARADD</i>) Account for More than 60% of Egyptian Ectodermal Dysplasia: A Report of Seven Novel Mutations |
| title_sort | gene mutations of the three ectodysplasin pathway key players i eda i i edar i and i edaradd i account for more than 60 of egyptian ectodermal dysplasia a report of seven novel mutations |
| topic | ectodysplasin A ectodermal eysplasia <i>EDA</i> <i>EDAR</i> <i>EDARADD</i> <i>WNT10A</i> |
| url | https://www.mdpi.com/2073-4425/12/9/1389 |
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