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

A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family

“…Till now, total nine families with EDSS1 and only one family with EDSS2 have been reported around the world; these included families were from Pakistan [ 10 – 12 , 15 , 20 ], Algeria and Italy [ 5 ], Afghanistan [ 22 ], and Turkey [ 14 , 21 ]. Using whole exome sequencing, we have identified a previously reported homozygous nonsense mutation p.(Gln61 ∗ ) in the NECTIN4 gene.…”

“…Earlier, this variant was reported by Raza et al in [ 11 ] in another family of Kashmiri origin; however, upon investigation, it was confirmed that both families had no evidence of relationship. According to the human genome mutation database (HGMD Professional 2023.4) and literature, only eleven mutations have been reported in NECTIN4, which include three nonsense (p.Asp61 ∗ , p.Gln77 ∗ , and p.Arg55 ∗ ), a frameshift (p.Pro304Hisfs ∗ 2), five missense (p.Pro212Arg, p.His83Tyr, p.Val242Met, p.Thr185Met, and p.Leu81Pro), an exon 2 deletion, and an apparent missense (p.Arg284Gln) inducing NECTIN4 splicing [ 5 , 11 , 14 , 15 , 22 ].…”

“…Till now, a limited number of mutations in the NECTIN4 gene have been reported in patients with EDSS1, and there is a lack of comprehensive genotype-phenotype associations. However, despite the diverse phenotypes of NECTIN4 mutations in EDSS1 patients and the lack of comprehensive genotype-phenotype associations, three clinical features, including cutaneous syndactyly, hair abnormalities, and dental anomalies, have been consistently observed in individuals with EDSS1, regardless of the ethnic background of patients [ 5 , 11 – 15 ].…”