A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1
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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.
Original language | English |
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Journal | Anais Brasileiros de Dermatologia |
Volume | 98 |
Issue number | 5 |
Pages (from-to) | 580-586 |
Number of pages | 7 |
ISSN | 0365-0596 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2023 Sociedade Brasileira de Dermatologia
- Ectodermal dysplasia, Ectodermal dysplasia syndactyly syndrome 1, Nectin cell adhesion molecule-4, Palmoplantar keratoderma, Poliovirus Receptor Related-4
Research areas
ID: 357580274