Alteration of Hair Melanin in Patients With Mowat-Wilson Syndrome: The Role of the ZEB2 Gene in Regulating Melanogenesis Through SLC45A2.

Mowat-Wilson syndrome (MOWS) is a congenital disease characterized by intellectual disability, delayed motor development, characteristic facial features, epilepsy, and a wide spectrum of neurocristopathies. MOWS is caused by de novo heterozygous loss-of-function mutations or deletions in the zinc finger E-box-binding homeobox2 (ZEB2) gene, which is a multifunctional regulator of neuronal development and cancer progression/metastasis through epithelial-to-mesenchymal transition. We recognized that patients with MOWS have brown to red hair. In the present study, we report that hair from patients with MOWS has reduced eumelanin and elevated pheomelanin contents, resulting in an increased pheomelanin-to-eumelanin ratio. Furthermore, ZEB2-mutated human epidermal melanocytes show a predominance of pheomelanin biosynthesis over eumelanin and decreased expression of SLC45A2, the gene responsible for oculocutaneous albinism 4. Our results suggest that ZEB2 plays a role in mixed melanogenesis by regulating the melanosomal ion transporter gene, SLC45A2.