Doroteya Raykova; Joakim Klar; Aysha Azhar; Tahir Naeem Khan; Naveed Altaf Malik; Muhammad Iqbal; Muhammad Tariq; Shahid Mahmood Baig; Niklas Dahl

“ The analysis of mouse digits showed a particularly strong staining in the region corresponding to the nail matrix, the nail bed and hyponychium. Interestingly, we observed an ordered monolayer of cells just adjacent to the nail plate with a strong keratin-74 staining, suggesting this protein to be of importance for the interphase of the nail and the nail bed. Furthermore, immunostaining of human skin sections revealed strong expression of Keratin-74 in the inner root sheath of hair follicles in healthy individuals. ”

“ Abstract Pure hair and nail ectodermal dysplasia (PHNED) comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR) PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. ”

“ The association between the p.Phe274Ser variant and AR PHNED is further supported by the absence of Keratin-74 staining in the hair follicles and epidermis of one patient suggesting the protein to be degraded, possibly as a consequence of absent dimerization. Our findings add to the phenotypic spectrum associated with KRT74 sequence variants, and further studies are now required to clarify the precise mechanisms mediated by both wild type and mutated Keratin-74 for the formation of keratin intermediate filament complexes of the hair shaft and nail plate. ”