176 Identification of putative phenotype-modifying genetic factors associated with phenotypic diversity in Brooke-Spiegler syndrome

Brooke-Spiegler syndrome (BSS; OMIM 605041) is a rare monogenic skin disease characterized by the development of appendage tumors caused mutations in cylindromatosis (CYLD) gene. Despite described phenotypes and reports underlying CYLD mutations, it has been difficult to establish genotype–phenotype correlations BSS. We recently investigated two BSS pedigrees (Hungarian with Bukovinian origin Anglo-Saxon), which affected family members exhibit striking differences their — despite carrying same disease-causing mutation (c.2806C>T, p.Arg936Ter) The aim our study was identify phenotype- modifying genetic factors further understanding In comparison whole exome sequencing data from Hungarian Anglo-Saxon patients, we have identified three putative phenotype-modifying variants: rs1053023 SNP signal transducer activator transcription 3 (STAT3) gene, rs1131877 tumor necrosis factor receptor-associated (TRAF3) gene rs202122812 neighbor BRCA1 1 (NBR1) Our contributes accumulating evidence for clinical importance factors, are potentially important elucidation prognosis.