Two Novel MBTPS2 Missense Mutations Impairing S2P Proteolytic Activity Lead to IFAP Syndrome With New Phenotypic Anomalies
October 2023
in “
Journal of dermatological science
”
MBTPS2 S2P proteolytic activity Ichthyosis follicularis alopecia photophobia IFAP syndrome Keratosis follicularis spinulosa decalvans Olmsted Syndrome follicular hyperkeratosis X-Linked Osteogenesis Imperfecta sterol regulating element binding protein SREBP signaling cholesterol homeostasis IFAP KFSD OS X-OI
TLDR New mutations in MBTPS2 reduce its function and cause IFAP syndrome with unusual symptoms.
The document discusses the role of the membrane-bound transcription factor site-2 protease (MBTPS2) in cholesterol homeostasis and its link to various disorders when mutated. These disorders include dermatological conditions such as Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome, Keratosis follicularis spinulosa decalvans (KFSD), and Olmsted Syndrome (OS), all characterized by follicular hyperkeratosis, absence of hair, and photophobia. Additionally, X-Linked Osteogenesis Imperfecta (X-OI), characterized by brittle bones, is also associated with MBTPS2 mutations. The mechanisms behind IFAP syndrome are not well understood, but it is suggested that impaired sterol regulating element binding protein (SREBP) signaling and growth under cholesterol-deficient conditions may contribute to MBTPS2-associated skin disorders. Understanding the functional significance of these variants is crucial for disease mechanisms and genotype-phenotype correlation.
