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Identification of putative phenotype‐modifying genetic factors associated with phenotypic diversity in Brooke‐Spiegler syndrome
Author(s) -
Pap Éva Melinda,
Farkas Katalin,
Széll Márta,
Németh Gábor,
Rajan Neil,
Nagy Nikoletta
Publication year - 2020
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.14161
Subject(s) - biology , phenotype , genetics , gene , pedigree chart , snp , exome sequencing , single nucleotide polymorphism , genotype
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 gene. We recently investigated a Hungarian and an Anglo‐Saxon pedigrees affected by Brooke‐Spiegler syndrome. Despite carrying the same disease‐causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene, the affected family members of the two pedigrees exhibit striking differences in their phenotypes. To identify phenotype‐modifying genetic factors, whole exome sequencing was performed and the data from the Hungarian and Anglo‐Saxon BSS patients were compared. Three putative phenotype‐modifying genetic variants were identified: the rs1053023 SNP of the signal transducer and activator of transcription 3 ( STAT3 ) gene, the rs1131877 SNP of the tumor necrosis factor receptor‐associated factor 3 ( TRAF3 ) gene and the rs202122812 SNP of the neighbour of BRCA1 gene 1 ( NBR1 ) gene. Our study contributes to the accumulating evidence for the clinical importance of phenotype‐modifying genetic factors, which are potentially important for the elucidation of disease prognosis.