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Novel TMC 8 splice site mutation in epidermodysplasia verruciformis and review of HPV infections in patients with the disease
Author(s) -
Imahorn E.,
Yüksel Z.,
Spoerri I.,
Gürel G.,
Imhof C.,
Saraçoğlu Z.N.,
Koku Aksu A.E.,
Rady P.L.,
Tyring S.K.,
Kempf W.,
Itin P.H.,
Burger B.
Publication year - 2017
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.14431
Subject(s) - epidermodysplasia verruciformis , genodermatosis , medicine , context (archaeology) , mutation , splice site mutation , dermatology , skin cancer , disease , cancer , cancer research , human papillomavirus , pathology , gene , genetics , rna splicing , biology , rna , paleontology
Background Epidermodysplasia verruciformis ( EV ) is a genodermatosis leading to infections with cutaneous HPV , persistent plane warts and a high rate of non‐melanoma skin cancer ( NMSC ). Biallelic loss‐of‐function mutations in TMC 6 and TMC 8 are known to be causative. Objective The aim of this study was to report EV ‐causing mutations in four patients with EV and to give an overview of all described patients with EV . Patients and methods We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and β‐ HPV s were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas ( cSCC ) and carcinomas in situ (Bowen type). We sequenced both TMC 6/8 for disease‐causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types. Results Three patients of one family carried a homozygous splice site mutation in TMC 8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC 6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV . Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC 6/8 . While β‐ HPV s were identified in the majority of cases, α‐ HPV s were detected in several individuals. Conclusion The relatively high proportion of EV patients without mutation in TMC 6/8 indicates the existence of EV ‐causing mutations in additional, presently unknown gene(s). However, a homozygous TMC 8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV ‐5 is the most commonly identified HPV in patients with EV , but HPV ‐3, HPV ‐14 and HPV ‐20 were unexpectedly identified more frequently than HPV ‐8.