title: Identification of LCK mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: S-L
authors.initials: SL
authors.lastname: Li
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing, China.|Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: L-N
authors.initials: LN
authors.lastname: Duo
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing, China.|Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: W
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing, China.|Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.
authors.forename: E-Y H
authors.initials: EH
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Xu
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Xiao
authors.affiliation: Department of Dermatology, General Hospital of Ningxia Medical University, Yinchuan, Ning Xia, China.
authors.forename: L
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, Ning Xia, China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Yang
authors.affiliation: Novogene Bioinformatics Technology Co., Ltd, Beijing, China.
authors.forename: L-T
authors.initials: LT
authors.lastname: Zheng
authors.affiliation: Novogene Bioinformatics Technology Co., Ltd, Beijing, China.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing, China.|Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Lin
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: H-N
authors.initials: HN
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: T-W
authors.initials: TW
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: C-L
authors.initials: CL
authors.lastname: Ma
authors.affiliation: Department of Dermatology, Peking University First Hospital, Beijing, China.|Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Li
mesh_terms: D000293:Adolescent; D004274:DNA, Recombinant / Q000235:genetics*; D004819:Epidermodysplasia Verruciformis / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics*; D010375:Pedigree; D012871:Skin Diseases / Q000235:genetics*; D055815:Young Adult
chemical_list: D004274:DNA, Recombinant; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)