Epidermodysplasia Verruciformis, Susceptibility To, 5

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Retrieved

2019-09-22

Source

Omim

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Genes

TMC6, TMC8, RHOH, IL7, CIB1, TP53, SLC30A1, STT3A, IGFALS, SOD1, CDKN2A, H3P10, SETD3, MIR25, UVRAG, LINC02605, VEGFA, CLEC4C, MIR214, SLC30A2, TP63, PDLIM7, RASGRP1, CKAP4, TEX11, CORO1A, NLRP3, FOXK1, SDCBP2, PYCARD, UBE2B, CD274, SLC39A13, SLC39A4, MIR210, ANGPT1, TTN, TNF, STS, CD36, CCR7, CRP, DYRK1A, ECM1, ERBB2, FCGR3A, FCGR3B, FLG, MTOR, GH1, IL2, IL10, ITK, IVL, LCK, MAS1, PPARG, PTEN, PTGS2, RMRP, RPE65, SCD, SREBF1, TM7SF2

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A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-5 (EV5) is conferred by homozygous mutation in the IL7 gene (146660) on chromosome 8q21. One such family has been reported.

Description

Epidermodysplasia verruciformis-5 is an autosomal recessive immunologic disorder characterized by onset of warts and verrucous or plaque-like skin lesions associated with HPV infection. Immunologic workup shows T-cell lymphopenia, particularly affecting CD4+ T cells. There is an increased risk of skin malignancy, and some patients may have other symptoms of immune dysfunction (summary by Horev et al., 2015).

For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).

Clinical Features

Horev et al. (2015) reported 3 adult sibs, born of consanguineous Arab parents, with EV5. All patients reported the onset of verrucous skin lesions in their twenties. One of the patients (patient 3) developed recurrent squamous cell carcinomas in early adulthood on sun-exposed areas, and 2 patients (patients 2 and 3) had a history of Cryptococcus neoformans meningitis after age 20 years. Skin samples taken from seborrheic keratosis-like, tinea versicolor-like, and verruca vulgaris-like lesions were positive for HPV3. Immunologic workup showed low total lymphocytes and severe T-cell lymphopenia affecting both CD4+ and CD8+ T cells, although 1 patient (patient 3) had normal CD8+ T-cell counts.

Inheritance

The transmission pattern of EV5 in the family reported by Horev et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 3 sibs, born of consanguineous Arab parents, with EV5, Horev et al. (2015) identified a homozygous nonsense mutation in the IL7 gene (R69X; 146660.0001). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Patient serum showed severely decreased or absent IL7 levels compared to controls. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. Patient serum levels of IL7 were very low or undetectable.