TY - JOUR

T1 - A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1

AU - Hajra, Bibi

AU - Abdullah, null

AU - Bibi, Nousheen

AU - Syed, Fibhaa

AU - Ullah, Asmat

AU - Ahmad, Wasim

AU - Umm-e-Kalsoom, null

N1 - Publisher Copyright: © 2023 Sociedade Brasileira de Dermatologia

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Ectodermal dysplasia

KW - Ectodermal dysplasia syndactyly syndrome 1

KW - Nectin cell adhesion molecule-4

KW - Palmoplantar keratoderma

KW - Poliovirus Receptor Related-4

U2 - 10.1016/j.abd.2022.07.009

DO - 10.1016/j.abd.2022.07.009

M3 - Journal article

C2 - 37183149

AN - SCOPUS:85159187766

VL - 98

SP - 580

EP - 586

JO - Anais Brasileiros de Dermatologia

JF - Anais Brasileiros de Dermatologia

SN - 0365-0596

IS - 5

ER -