A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1
Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECT...
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Sociedade Brasileira de Dermatologia
2023-08-01
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| Series: | Anais Brasileiros de Dermatologia |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962023000500580&lng=en&tlng=en |
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| author | Bibi Hajra Abdullah Nousheen Bibi Fibhaa Syed Asmat Ullah Wasim Ahmad Umm-e-Kalsoom |
| author_facet | Bibi Hajra Abdullah Nousheen Bibi Fibhaa Syed Asmat Ullah Wasim Ahmad Umm-e-Kalsoom |
| author_sort | Bibi Hajra |
| collection | DOAJ |
| description | Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families. |
| first_indexed | 2024-03-12T12:33:09Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-12T12:33:09Z |
| publishDate | 2023-08-01 |
| publisher | Sociedade Brasileira de Dermatologia |
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| series | Anais Brasileiros de Dermatologia |
| spelling | doaj.art-9da5350d3906421fa84ae0ce4524d6bc2023-08-29T07:43:17ZengSociedade Brasileira de DermatologiaAnais Brasileiros de Dermatologia0365-05962023-08-0198558058610.1016/j.abd.2022.07.009A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1Bibi Hajrahttps://orcid.org/0000-0002-8796-0746 Abdullahhttps://orcid.org/0000-0003-4320-5746Nousheen Bibihttps://orcid.org/0000-0001-8399-0932Fibhaa Syedhttps://orcid.org/0000-0002-9053-8407Asmat Ullahhttps://orcid.org/0000-0002-5715-3425Wasim Ahmadhttps://orcid.org/0000-0003-1541-7258 Umm-e-Kalsoomhttps://orcid.org/0000-0002-6842-3558Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962023000500580&lng=en&tlng=enEctodermal dysplasiaPalmoplantar keratodermaPoliovirus Receptor Related-4Nectin cell adhesion molecule-4Ectodermal dysplasia syndactyly syndrome 1 |
| spellingShingle | Bibi Hajra Abdullah Nousheen Bibi Fibhaa Syed Asmat Ullah Wasim Ahmad Umm-e-Kalsoom A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1 Anais Brasileiros de Dermatologia Ectodermal dysplasia Palmoplantar keratoderma Poliovirus Receptor Related-4 Nectin cell adhesion molecule-4 Ectodermal dysplasia syndactyly syndrome 1 |
| title | A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1 |
| title_full | A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1 |
| title_fullStr | A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1 |
| title_full_unstemmed | A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1 |
| title_short | A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1 |
| title_sort | novel homozygous nonsense mutation in nectin4 gene in a pakistani family with ectodermal dysplasia syndactyly syndrome 1 |
| topic | Ectodermal dysplasia Palmoplantar keratoderma Poliovirus Receptor Related-4 Nectin cell adhesion molecule-4 Ectodermal dysplasia syndactyly syndrome 1 |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962023000500580&lng=en&tlng=en |
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