A Homozygous Missense Variant in Type I Keratin KRT25 Causes Autosomal Recessive Woolly Hair

The study identified a homozygous missense variant c.950T>C (p.(Leu317Pro)) in the KRT25 gene as the cause of autosomal recessive woolly hair (ARWH) in two unrelated consanguineous Pakistani families. This variant was found to disrupt the second α-helical rod domain of the KRT25 protein, potentially affecting its interaction with type II keratins in the hair follicle's inner root sheath and hair shaft medulla. The findings highlighted the role of IRS-specific type I keratins in hair follicle development and maintenance, aligning with observations of similar hair abnormalities in mice with Krt25 mutations. The study provided new insights into the genetic basis of human hair abnormalities.