Loss-Of-Function Mutations In HOXC13 Cause Pure Hair And Nail Ectodermal Dysplasia

The study identified loss-of-function mutations in the HOXC13 gene as a cause of autosomal-recessive pure hair and nail ectodermal dysplasia (PHNED) in two consanguineous families of different ethnic origins. In a Chinese family, a homozygous nonsense mutation in HOXC13 was found, while an Afghan family exhibited a 27.6 kb homozygous microdeletion involving the first exon of HOXC13. These mutations led to significantly reduced HOXC13 mRNA levels and nearly absent protein staining in hair follicles, indicating a mechanism of nonsense-mediated mRNA decay. The findings highlighted the critical role of HOXC13 in hair and nail development, as affected individuals showed congenital atrichia and severe nail dystrophy.