Identification of LCK mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma
Identification of LCK mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma
复制标题
伴有 T 细胞缺陷和病毒诱导鳞状细胞癌的非典型疣状表皮发育不良家系中 LCK 突变的鉴定
DOI：
10.1111/bjd.14679
复制
发表时间：
2016-12-01
影响因子：
10.3
通讯作者：
Li, C. -Y.
中科院分区：
文献类型：
--
作者：
Li, S. -L.;Duo, L. -N.;Li, C. -Y.
背景遗传性疣状表皮发育不良(EV)是一种罕见的皮肤病，其特征是对特定类型的人乳头瘤病毒(HPV)易感性，并与皮肤癌密切相关。EV的大多数病例是由Ever1/EveR2基因的失活突变引起的。然而，更多与EV相关但不同于EV的表型被报道为免疫缺陷状态，但没有发生1/EveR2突变，这些非典型EV病例的遗传学基础尚不清楚。目的确定3个非典型EV感染但无1/EveR2突变的兄弟姐妹的致病基因。方法采用全外显子测序和Sanger测序相结合的方法对纳入研究的非典型EV患者的致病基因进行分析。结论在一个伴有T细胞缺陷、HPV感染和病毒诱导恶性病变的非典型EV家系中发现了一种新的LCK突变，为了解宿主对HPV的防御机制提供了新的线索，并为EV表型患者的遗传咨询提供了新的线索。
Background Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood. Objectives To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation.Methods Whole-exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study.Results A homozygous splicing mutation was detected in LCK (c.188-2A>G). This mutation resulted in an exon 3 deletion T lymphocyte-specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay.Conclusions We demonstrate a novel mutation in LCK in a family affected by atypical EV with T-cell defects, HPV infection and virus-induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype.