Abstract
Brooke-Spiegler syndrome (BSS; OMIM 605041) is a rare monogenic skin disease characterized by the development of skin appendage tumors caused by mutations in the cylindromatosis (CYLD) gene. Despite the described phenotypes and reports of the underlying CYLD mutations, it has been difficult to establish genotype–phenotype correlations in BSS. We recently investigated two BSS pedigrees (Hungarian with Bukovinian origin and Anglo-Saxon), in which the affected family members exhibit striking differences in their phenotypes — despite carrying the same disease-causing mutation (c.2806C>T, p.Arg936Ter) of the CYLD gene.
Highlights
Tyne, Newcastle, United Kingdom and 5 MTA-SZTE, Dermatological Research Group, Eotvos Lorand Research Network, Szeged, Hungary Recently described Hungarian and Anglo-Saxon pedigrees that are affected by CYLD cutaneous syndrome (syn: Brooke-Spiegler syndrome (BSS)) carry the same disease-causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene but exhibit striking phenotypic differences
The microglial decreased phagocytosis in olfactory bulb is responsible for neuropsychiatric disorders in tuberous sclerosis complex model mice MK Kumagai1, M Fujimoto2 and MW Kaneda1 1 Department of Neurocutaneous Medicine, Division of Health Sciences, Graduate School of Medicine, Osaka University, Suita, Japan and 2 Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Japan Tuberous sclerosis complex (TSC) is a multi-system genetic disorder associated with a variety of physical manifestations caused by mutations in TSC1 or TSC2, which encode proteins that negatively regulate mTOR complex 1
We found that the intraperitoneal mTOR inhibitor Sirolimus reduced neuropsychiatric symptoms in these cKO mice and significantly changed the microglial morphology of the glomerulus of the olfactory to that with extended protrusions in cKO mice, on the other hand the morphology of microglia without sirolimus was almost the same between cKO and control mice
Summary
Newcastle, United Kingdom and 5 MTA-SZTE, Dermatological Research Group, Eotvos Lorand Research Network, Szeged, Hungary Recently described Hungarian and Anglo-Saxon pedigrees that are affected by CYLD cutaneous syndrome (syn: Brooke-Spiegler syndrome (BSS)) carry the same disease-causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene but exhibit striking phenotypic differences. To generalize this concept we broadened our investigations and included other e newly identified and already described e disease causing CYLD mutations and are currently working on clarifying their effect together with elevated TRAF3 and NBR1 levels on NF-kB activity.
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