Identification of<i>LCK</i>mutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma

Li, S.-L.; Duo, Lina; Wang, H.-J.; Dai, Wei; Zhou, Eray Yihui; Xü, Ying; Zhao, Tao; Xiao, Yunfeng; Li, Xia; Yang, Zhijuan; Zheng, Lei; Hu, Y.-Y.; Lin, Zheguang; Wang, H.-N.; Gao, Tianwen; Ma, Chun-Yan; Yang, Yanling; Li, C.-Y.

doi:10.1111/bjd.14679

Cited by 29 publications

(22 citation statements)

References 18 publications

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“…LCK deficiency causes atypical EV with CD4 T cell deficiency as well as recurrent pneumonia and severe warts complicated by non-melanoma skin cancer (45). To date, only a single patient with LCK deficiency has been described, leading to uncertainty in the full spectrum of infectious susceptibility.…”

Section: Lck Deficiencymentioning

confidence: 99%

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

2017

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Viral infections are commonplace and often innocuous. Nevertheless, within the population of patients with primary immunodeficiencies (PIDDs), viral infections can be the feature that drives a diagnostic evaluation or can be the most significant morbidity for the patient. This review is focused on the viral complications of PIDDs. It will focus on respiratory viruses, the most common type of viral infection in the general population. Children and adults with an increased frequency or severity of respiratory viral infections are often referred for an immunologic evaluation. The classic teaching is to investigate humoral function in people with recurrent sinopulmonary infections, but this is often interpreted to mean recurrent bacterial infections. Recurrent or very severe viral infections may also be a harbinger of a primary immunodeficiency as well. This review will also cover persistent cutaneous viral infections, systemic infections, central nervous system infections, and gastrointestinal infections. In each case, the specific viral infections may drive a diagnostic evaluation that is specific for that type of virus. This review also discusses the management of these infections, which can become problematic in patients with PIDDs.

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Section: Lck Deficiencymentioning

confidence: 99%

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

2017

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“…Indeed, the skin lesions develop early in life and are caused by the same beta-HPV subtypes that are found in patients with typical EV (see Table 1 ). The other clinical phenotypes, mostly infectious and auto-immune, differ between patients ( Crequer et al, 2012a , b ; Sanal et al, 2012 ; Stray-Pedersen et al, 2014 ; Stepensky et al, 2015 ; Li et al, 2016 ; Platt et al, 2017 ; Tahiat et al, 2017 ). The clinical features of patients with atypical EV are reviewed in Table 1 .…”

Section: Clinical Manifestations Of Atypical Evmentioning

confidence: 99%

Epidermodysplasia Verruciformis: Inborn Errors of Immunity to Human Beta-Papillomaviruses

et al. 2018

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Epidermodysplasia verruciformis (EV) is an autosomal recessive skin disorder with a phenotype conditional on human beta-papillomavirus (beta-HPV) infection. Such infections are common and asymptomatic in the general population, but in individuals with EV, they lead to the development of plane wart-like and red or brownish papules or pityriasis versicolor-like skin lesions, from childhood onwards. Most patients develop non-melanoma skin cancer (NMSC), mostly on areas of UV-exposed skin, from the twenties or thirties onwards. At least half of the cases of typical EV are caused by biallelic loss-of-function mutations of TMC6/EVER1 or TMC8/EVER2. The cellular and molecular basis of disease in TMC/EVER-deficient patients is unknown, but a defect of keratinocyte-intrinsic immunity to beta-HPV is suspected. Indeed, these patients are not susceptible to other infectious diseases and have apparently normal leukocyte development. In contrast, patients with an atypical form of EV due to inborn errors of T-cell immunity invariably develop clinical symptoms of EV in the context of other infectious diseases. The features of the typical and atypical forms of EV thus suggest that the control of beta-HPV infections requires both EVER1/EVER2-dependent keratinocyte-intrinsic immunity and T cell-dependent adaptive immunity.

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“…Defects in the structure or barrier function of the skin may allow exogenous stressor permeation into the deeper layers of the skin, further stimulating the existing genetic instability, progression to dysplasia, and cancer development. Similarly, in these individuals, the skin is a target organ for viral infection (including but not limited to HPV), as seen in other skin fragility conditions with increased SCC development, where reduced T cell numbers allow HPV to overcome host defenses and contribute to malignancy [ 91 , 92 ]. In the FA-deficient HPV immortalized epidermis, an increased epithelial hyperplasia was observed suggesting a role for the FA pathway in the maintenance of alternative epithelial properties, such as its structure and cell cycle control for the prevention of HPV-associated SCCs [ 50 ].…”

Section: Epidermal Abnormalities In Fanconi Anemiamentioning

confidence: 99%

Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

Khoury

Sauter

Kovacic

et al. 2018

Viruses

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Human papillomavirus (HPV) infections cause a significant proportion of cancers worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin. High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal tract. HPV oncogene activities and the biology of SCCs have been intensely studied in laboratory models and humans. What remains largely unknown are host tissue and immune-related factors that determine an individual’s susceptibility to infection and/or carcinogenesis. Such susceptibility factors could serve to identify those at greatest risk and spark individually tailored HPV and SCC prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that is in part characterized by extreme susceptibility to SCCs. An increased prevalence of HPV has been reported in affected individuals, and molecular and functional connections between FA, SCC, and HPV were established in laboratory models. However, the presence of HPV in some human FA tumors is controversial, and the extent of the etiological connections remains to be established. Herein, we discuss cellular, immunological, and phenotypic features of FA, placed into the context of HPV pathogenesis. The goal is to highlight this orphan disease as a unique model system to uncover host genetic and molecular HPV features, as well as SCC susceptibility factors.

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Identification ofLCKmutation in a family with atypical epidermodysplasia verruciformis with T-cell defects and virus-induced squamous cell carcinoma

Abstract: 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.

Cited by 29 publications

References 18 publications

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

Recurrent and Sustained Viral Infections in Primary Immunodeficiencies

Epidermodysplasia Verruciformis: Inborn Errors of Immunity to Human Beta-Papillomaviruses

Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know

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