A nonsense variant in KRT31 is associated with autosomal dominant monilethrix.

This article focuses on the identification of a pathogenic variant in the KRT31 gene as a novel cause of autosomal dominant monilethrix, a rare hereditary hair disorder characterized by beaded hair shafts and increased fragility. The study analyzed nine affected individuals from four unrelated German families who lacked mutations in previously known monilethrix genes (KRT81, KRT83, KRT86, and DSG4) and found a nonsense variant c.1081G>T; p.(Glu361*) in KRT31. Functional cellular assays demonstrated that this mutant keratin 31 protein forms abnormal vesicular-like structures near the cell membrane and shows impaired co-localization with its binding partner keratin 85, suggesting disrupted intermediate filament assembly. This discovery expands the genetic spectrum of monilethrix and supports including KRT31 in diagnostic gene panels to improve molecular diagnosis and genetic counseling for affected individuals.