A Missense Mutation Within the Helix Termination Motif of KRT25 Causes Autosomal Dominant Woolly Hair/Hypotrichosis

The study identified a novel missense mutation in the KRT25 gene, c.712G>T (p.Val238Leu), as the cause of autosomal-recessive hypotrichosis with woolly hair in individuals from the Volga-Ural region of Russia. This mutation, found in a highly conserved position of type I keratin KRT25, disrupted keratin intermediate filament formation, affecting hair structure and density. The research involved 119 affected individuals and 300 phenotypically normal individuals, revealing several heterozygous carriers but no homozygous individuals among the controls. The findings suggested a founder effect in these isolated populations and expanded the understanding of genetic causes behind hair growth disorders, particularly those involving keratin genes.

The study investigated woolly hair (WH) in two consanguineous Pakistani families and identified a homozygous missense variant c.950T>C (p.(Leu317Pro)) in the KRT25 gene as the cause of autosomal recessive WH. This variant was found to disrupt the protein structure, potentially affecting the interaction with type II keratins in the hair follicle, leading to the characteristic tightly curled hair. The findings highlighted a novel gene involved in hair abnormalities and supported the role of type I keratins in hair follicle development and hair texture maintenance.

The document discussed the critical role of keratins in hair structure and disorders, highlighting their function in forming intermediate filaments essential for hair and skin integrity. It detailed how mutations in specific keratin genes, such as KRT81, KRT83, and KRT86, lead to hair disorders like monilethrix, characterized by fragile, beaded hair. The study by van Steensel et al. expanded the mutation spectrum of monilethrix by identifying additional cases linked to KRT83 mutations, reinforcing its role in the disorder. The variability in hair phenotype among monilethrix patients remained unexplained, suggesting further research into other hair cortex components could provide insights into hair strength and structure.

The study identified a missense mutation, c.422T>G (p.Phe141Cys), in the KRT71 gene as the cause of autosomal dominant woolly hair and hypotrichosis in a Japanese family. This mutation disrupted keratin intermediate filament formation, highlighting the role of IRS-specific keratins in hair follicle development. The mutation was not found in 200 healthy controls, indicating its pathogenic nature. The findings expanded the understanding of hereditary hair disorders, particularly non-syndromic forms of woolly hair, and emphasized the importance of the inner root sheath in hair follicle structure.