Epidermodysplasia Verruciformis, Susceptibility To, 2

A number sign (#) is used with this entry because of evidence that susceptibility to epidermodysplasia verruciformis-2 (EV2) is conferred by homozygous mutation in the TMC8 gene (605829) gene on chromosome 17q25.

Description

Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000).

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

Clinical Features

Ramoz et al. (2002) described 5 families, including 3 (A1, A2, and C1) that were previously reported (Ramoz et al., 1999), with epidermodysplasia verruciformis. Patients had early onset of the disease, a disseminated infection by EV-specific HPV genotypes, including at least one of the potentially oncogenic genotypes (HPV types 5, 8, 14, 17, or 20), and lesions of the skin showing the cytopathic effect pathognomonic of EV. Significant variations were observed, however, in the HPV genotypes detected, the extension of the lesions and the development of skin carcinomas. HPV5, the genotype most frequently associated with EV cancers, was detected only in families A1, A2, and C1, whereas the less oncogenic HPV20, an HPV5-related genotype, was found in all 5 families.

Imahorn et al. (2017) reported 3 Turkish sibs, aged 12, 17, and 18 years, who developed plane (flat) warts during early childhood. Histopathologic analysis showed the presence of blue cells, confirming the diagnosis of EV. Infections with beta-HPV5 and beta-HPV9 were detected in all 3 patients' warts. Family history revealed that 2 aunts and 1 uncle were also affected.

Mapping

In Algerian and Colombian consanguineous families segregating EV, Ramoz et al. (2000) mapped the disorder to a 1-cM interval on chromosome 17q25.

Molecular Genetics

In affected members of consanguineous Colombian and Algerian families with EV mapped to chromosome 17q25, Ramoz et al. (2002) identified 2 homozygous nonsense mutations in the EVER1 gene (TMC6; 605828.0001-605828.0002) and 2 homozygous mutations in the EVER2 gene (TMC8; 605829.0001-605829.0002).

In a Turkish family with EV, Imahorn et al. (2017) analyzed the TMC6 and TMC8 genes, and identified homozygosity for a splice site mutation in the TMC8 gene (605829.0003) that segregated fully with disease.