Abstract
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.
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Acknowledgements
We would like to thank the family members for agreeing to participate in the study. We like to thank Dr. Mirvat Sibai for providing us with the ER marker and Ms. Inaam El Rassi for the technical support. This work was funded by MPP and URB grants to Mazen kurban from the American University of Beirut and a grant from the Lebanese National Council for Scientific Research.
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This study was funded by MPP and URB grants to Mazen kurban from the American University of Beirut and a grant from the Lebanese National Council for Scientific Research.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Nemer, G., Safi, R., Kreidieh, F. et al. Understanding the phenotypic similarities between IFAP and Olmsted syndrome from a molecular perspective: the interaction of MBTPS2 and TRPV3. Arch Dermatol Res 309, 637–643 (2017). https://doi.org/10.1007/s00403-017-1762-z
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DOI: https://doi.org/10.1007/s00403-017-1762-z