A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family
EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasi...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Genetics Research |
| Online Access: | http://dx.doi.org/10.1155/2023/9999660 |
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| author | Ghazanfar Ali Sadia Sadia Syeda Ain-ul- Batool Zahid Azeem Naheed Bashir Awan Syed Akif Raza Kazmi Zia- Ur- Rehman Zeeshan Anjum Fazal- Ur- Rehman Abdul Wali Kafaitullah Khan Nasib Zaman Muhammad Ayub Muhammad Sajid Noor Hassan |
| author_facet | Ghazanfar Ali Sadia Sadia Syeda Ain-ul- Batool Zahid Azeem Naheed Bashir Awan Syed Akif Raza Kazmi Zia- Ur- Rehman Zeeshan Anjum Fazal- Ur- Rehman Abdul Wali Kafaitullah Khan Nasib Zaman Muhammad Ayub Muhammad Sajid Noor Hassan |
| author_sort | Ghazanfar Ali |
| collection | DOAJ |
| description | EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1. |
| format | Article |
| id | doaj-art-f0de4b1c26c54d1183a65e7a40404756 |
| institution | Kabale University |
| issn | 1469-5073 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Genetics Research |
| spelling | doaj-art-f0de4b1c26c54d1183a65e7a404047562025-02-03T06:43:11ZengWileyGenetics Research1469-50732023-01-01202310.1155/2023/9999660A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri FamilyGhazanfar Ali0Sadia Sadia1Syeda Ain-ul- Batool2Zahid Azeem3Naheed Bashir Awan4Syed Akif Raza Kazmi5Zia- Ur- Rehman6Zeeshan Anjum7Fazal- Ur- Rehman8Abdul Wali9Kafaitullah Khan10Nasib Zaman11Muhammad Ayub12Muhammad Sajid13Noor Hassan14Department of BiotechnologyDepartment of BiotechnologyDepartment of BiotechnologyDepartment of BiochemistryDepartment of BiotechnologyDepartment of ChemistryPir Mehr Ali Shah Arid Agriculture UniversityDepartment of BiotechnologyDepartment of MicrobiologyDepartment of BiotechnologyDepartment of MicrobiologyCentre for Biotechnology and Microbiology University of SwatInstitute of BiochemistryDepartment of PathologyInstitute of BiochemistryEDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.http://dx.doi.org/10.1155/2023/9999660 |
| spellingShingle | Ghazanfar Ali Sadia Sadia Syeda Ain-ul- Batool Zahid Azeem Naheed Bashir Awan Syed Akif Raza Kazmi Zia- Ur- Rehman Zeeshan Anjum Fazal- Ur- Rehman Abdul Wali Kafaitullah Khan Nasib Zaman Muhammad Ayub Muhammad Sajid Noor Hassan A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family Genetics Research |
| title | A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family |
| title_full | A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family |
| title_fullStr | A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family |
| title_full_unstemmed | A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family |
| title_short | A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family |
| title_sort | recurrent nonsense mutation in nectin4 underlying ectodermal dysplasia syndactyly syndrome with a novel phenotype in a consanguineous kashmiri family |
| url | http://dx.doi.org/10.1155/2023/9999660 |
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