Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia: Allelism with Dominant Woolly Hair/Hypotrichosis

The study investigated a consanguineous Pakistani family with autosomal recessive pure hair and nail ectodermal dysplasia (AR PHNED) and identified a rare homozygous c.821T>C variant (p.Phe274Ser) in the KRT74 gene. This mutation, which affects the stability of keratin intermediate filaments, was linked to the condition in the family, as confirmed by immunohistochemical analyses showing loss of Keratin-74 expression in affected individuals. This was the first time a KRT74 missense variant was associated with AR PHNED, expanding the known phenotypic spectrum of KRT74 mutations, which were previously linked to autosomal dominant woolly hair/hypotrichosis simplex (ADWH).