Understanding the phenotypic similarities between IFAP and Olmsted syndrome from a molecular perspective: the interaction of MBTPS2 and TRPV3

• Published in: Archives of Dermatological Research 2017-10, Vol.309 (8), p.637-643
• Main Authors: Nemer, Georges, Safi, Rémi, Kreidieh, Firas, Usta, Julnar, Bergqvist, Christina, Ballout, Farah, Btadini, Waed, Hamzeh, Nour, Abbas, Ossama, Kibbi, Abdul Ghani, Shimomura, Yutaka, Kurban, Mazen
• Format: Article
• Language: English
• Subjects: Adolescent; Alopecia - genetics; Alopecia - pathology; Cell death; Child; Dermatology; Gene Expression Regulation - physiology; Genetic disorders; HEK293 Cells; HeLa Cells; Humans; Ichthyosis; Ichthyosis - genetics; Ichthyosis - pathology; Male; Medicine; Medicine & Public Health; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Mutagenesis, Site-Directed; Mutation; Original Paper; Peptidase; Photophobia - genetics; Photophobia - pathology; Rare Diseases; Signal transduction; Transient receptor potential proteins; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s00403-017-1762-z

Ichthyosis Follicularis, Atrichia, and Photophobia (IFAP) is a severe rare genetic disorder caused by mutations in the gene encoding the Membrane-Bound Transcription Factor Peptidase, Site 2 (MBTPS2). Olmsted syndrome is another rare genetic disease with overlapping clinical features caused by mutations in the gene encoding the Transient Receptor Potential Cation Channel, subfamily V (TRPV3). Mutations in MBTPS2 have been recently reported in Olmsted syndrome, underscoring the overlap and the confusion in separating Olmsted from IFAP syndrome. We studied a Lebanese family with IFAP syndrome both, clinically and molecularly, and investigated whether there is a cross relation between TRPV3 and MBTPS2. We identified a recurrent mutation designated p.F475S in MBTPS2 in the affected individuals. This mutation was not found in 100 control individuals from the same population. We determined that TRPV3 regulatory region is a target for MBTPS2. In addition, there was an increased cell death in the cells transfected with the mutant versus the wild-type MBTPS2. In conclusion, we identified a direct regulatory effect of MBTPS2 on TRPV3 which can partially contribute to the overlapping clinical features of IFAP and Olmsted syndromes under a common signaling pathway.