Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity
Ectodermal dysplasia (ED) are hereditary disorders characterized by the disturbance of the ectodermal development of at least two of four ectodermal tissues: teeth, hair, nails and sweat glands. Clinical classification of ED is challenged by overlapping features, variable expressivity, and low numbe...
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MDPI AG
2022-06-01
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| author | Eman A. Rabie Inas S. M. Sayed Khalda Amr Hoda A. Ahmed Mostafa I. Mostafa Nehal F. Hassib Heba El-Sayed Suher K. Zada Ghada El-Kamah |
| author_facet | Eman A. Rabie Inas S. M. Sayed Khalda Amr Hoda A. Ahmed Mostafa I. Mostafa Nehal F. Hassib Heba El-Sayed Suher K. Zada Ghada El-Kamah |
| author_sort | Eman A. Rabie |
| collection | DOAJ |
| description | Ectodermal dysplasia (ED) are hereditary disorders characterized by the disturbance of the ectodermal development of at least two of four ectodermal tissues: teeth, hair, nails and sweat glands. Clinical classification of ED is challenged by overlapping features, variable expressivity, and low number of patients, hindering full phenotypic spectrum identification. Disease-causing variants in elements of major developmental pathways, e.g., Ectodysplasin/NFκB, Wnt, and Tp63 pathways, have been identified in fewer than half of ED phenotypes. Whole-exome sequencing (WES) was performed for ten Egyptian ED patients presenting with tooth agenesis, normal sweating, scalp hypotrichosis, and sharing characteristic facial features. WES was followed by in silico analysis of the effects of novel detected genetic variants on mRNA and protein structure. The study identified four novel rare pathogenic and likely pathogenic <i>TSPEAR</i> variants, a gene which was recently found to be involved in ectodermal organogenesis. A novel in-frame deletion recurred in eight patients from six unrelated families. Comparing our cohort to previously reported <i>TSPEAR</i> cohorts highlighted the influence of ethnicity on <i>TSPEAR</i> phenotypic affection. Our study expands the clinical and mutational spectrum of the growing <i>TSPEAR</i> associated phenotypes, and pinpoints the influence of WES and in silico tools on identification of rare disease-causing variants. |
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| last_indexed | 2024-03-09T23:43:08Z |
| publishDate | 2022-06-01 |
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| series | Genes |
| spelling | doaj.art-b4d30de5a13048a1baebbdc99721e9eb2023-11-23T16:48:33ZengMDPI AGGenes2073-44252022-06-01136105610.3390/genes13061056Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of EthnicityEman A. Rabie0Inas S. M. Sayed1Khalda Amr2Hoda A. Ahmed3Mostafa I. Mostafa4Nehal F. Hassib5Heba El-Sayed6Suher K. Zada7Ghada El-Kamah8Medical 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, EgyptMedical Molecular 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, EgyptClinical 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, EgyptClinical Genetics Department, Human Genetics & Genome Research Division (HGGR), National Research Centre (NRC), Cairo 12622, EgyptEctodermal dysplasia (ED) are hereditary disorders characterized by the disturbance of the ectodermal development of at least two of four ectodermal tissues: teeth, hair, nails and sweat glands. Clinical classification of ED is challenged by overlapping features, variable expressivity, and low number of patients, hindering full phenotypic spectrum identification. Disease-causing variants in elements of major developmental pathways, e.g., Ectodysplasin/NFκB, Wnt, and Tp63 pathways, have been identified in fewer than half of ED phenotypes. Whole-exome sequencing (WES) was performed for ten Egyptian ED patients presenting with tooth agenesis, normal sweating, scalp hypotrichosis, and sharing characteristic facial features. WES was followed by in silico analysis of the effects of novel detected genetic variants on mRNA and protein structure. The study identified four novel rare pathogenic and likely pathogenic <i>TSPEAR</i> variants, a gene which was recently found to be involved in ectodermal organogenesis. A novel in-frame deletion recurred in eight patients from six unrelated families. Comparing our cohort to previously reported <i>TSPEAR</i> cohorts highlighted the influence of ethnicity on <i>TSPEAR</i> phenotypic affection. Our study expands the clinical and mutational spectrum of the growing <i>TSPEAR</i> associated phenotypes, and pinpoints the influence of WES and in silico tools on identification of rare disease-causing variants.https://www.mdpi.com/2073-4425/13/6/1056<i>TSPEAR</i>ectodermal dysplasiatooth agenesisdysmorphic facial featuresgenetics of North Africa |
| spellingShingle | Eman A. Rabie Inas S. M. Sayed Khalda Amr Hoda A. Ahmed Mostafa I. Mostafa Nehal F. Hassib Heba El-Sayed Suher K. Zada Ghada El-Kamah Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity Genes <i>TSPEAR</i> ectodermal dysplasia tooth agenesis dysmorphic facial features genetics of North Africa |
| title | Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity |
| title_full | Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity |
| title_fullStr | Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity |
| title_full_unstemmed | Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity |
| title_short | Confirmation of a Phenotypic Entity for <i>TSPEAR</i> Variants in Egyptian Ectodermal Dysplasia Patients and Role of Ethnicity |
| title_sort | confirmation of a phenotypic entity for i tspear i variants in egyptian ectodermal dysplasia patients and role of ethnicity |
| topic | <i>TSPEAR</i> ectodermal dysplasia tooth agenesis dysmorphic facial features genetics of North Africa |
| url | https://www.mdpi.com/2073-4425/13/6/1056 |
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