Identification of the LCK mutation in an atypical epidermodysplasia verruciformis family with T cell defects and virus-induced squamous cell carcinoma

Summary

Background

Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPVs) and is strongly associated with skin carcinomas. Inactivating mutations in EVER1/2 account for most EV patients. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/2 mutation, and the genetic basis for these atypical EV cases is poorly understood.

Objective

The aim of this study is to identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/2 mutation.

Methods

Whole exome sequencing (WES) followed by Sanger sequencing was performed to identify the gene responsible for the atypical EV patients enrolled in our study.

Results

A homozygous splicing mutation was detected in the T lymphocyte-specific protein tyrosine kinase (LCK) gene (c.188-2A>G). And this mutation resulted in an exon 3-deletion LCK isoform, which further led to frameshift mutation and subsequent mRNA decay.

Conclusion

Our study demonstrates a novel mutation in LCK in an atypical EV-affected family with T cell defects, HPV infection and virus-induced malignancy, which provides new clues for the understanding of host defenses against HPV and better genetic counseling of patients with EV phenotype.

This article is protected by copyright. All rights reserved.

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1Tehwvu
via IFTTT