Identification of a novel missense variant in the

Background: Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by the variants of the Methods: Clinical data and peripheral blood samples were collected from the affected family. Whole-exome sequencing (WES) was conducted to identify potential pathogenic variants, followed by Sanger sequencing to validate the candidate variant. Bioinformatic tools were employed to predict the 3D structure alterations and pathogenicity of the variant. Wild-type and mutant Results: The proband presented with clinical manifestations, including nail malformation, patella dysplasia, restricted elbow movement, and pes planus. Both his mother and sister exhibited symptoms related to the skeletal system. WES identified a novel c.812G>C (p.R271T) variant in the affected family members. Bioinformatic analyses revealed structural modification in the protein and predicted functional impairment. Western blotting showed no significant difference in the expression level between wild-type and mutant protein. However, immunofluorescence demonstrated distinct changes in the subcellular localization of c.812G>C mutant. Conclusion: NPS is a rare multisystem disorder with variable clinical presentations. In this family, the skeletal system was mainly involved with variations among different members. Our study identified a novel c.812G > c variant in the