A novel pathogenic variant in the FZD6 gene causes recessive nail dysplasia in a large Iranian kindred

摘要: Abstract Background Nail disorder nonsyndromic congenital (NDNC) is a very rare clinically and genetically heterogeneous disease inherited both in recessive or dominant modes. FZD6 component of Wnt-FZD signaling pathway which loss-of-function variants the corresponding genes could lead to nail anomalies. Objective A large multiplex family with NDNC was referred for genetic counselling. Thorough evaluation performed. Methods PCR-Sanger sequencing carried out coding exons exon-intron boundaries gene. Co-segregation analysis, silico computational protein modeling accomplished. Results homozygous 1 bp deletion variant, c.1859delC (p.Ser620Cysfs*75), leading truncating found patient. Parents were heterozygous variant. The variant be co-segreagting phenotype family. Computational analysis revealed its pathogenic consequence by disturbing cytoplasmic domain structure through loss phosphorylation residues. met criteria being according ACMG guideline. Conclusions This first report diagnosis Iran. We also novel study gene recommended as step diagnostic routing autosomal patients enlarged nails.