A novel homozygous mutation of the EVER1/TMC6 gene in a Japanese patient with epidermodysplasia verruciformis

Conflicts of interest: none declared. S.A. and G.N. contributed equally to this study. Epidermodysplasia verruciformis (EV; OMIM 226400) is a rare, autosomal recessive genetic disease characterized by abnormal susceptibility to disease‐specific human papillomaviruses (HPVs). Patients with EV have usually presented with skin lesions resembling disseminated flat warts or pityriasis versicolor since childhood. Some of the lesions may progress to skin cancers late in life. Recently, genetic susceptibility loci for EV were mapped to chromosomes 2p21–24 and 17q25.1 Two different genes, EVER1/TMC6 and EVER2/TMC8, were identified in chromosome 17q25.2 We report a woman with HPV type 12‐induced EV who carried a homozygous C→T transition at nucleotide position 220 within exon 4 of EVER1 that led to a premature translation termination. A 57‐year‐old woman presented with a 46‐year history of multiple, scaly erythematous plaques on her neck, trunk and extremities (Fig. 1a). There was consanguinity between the patient’s parents. Of her five siblings, a brother had died soon after birth, and two sisters had died of uncertain causes at the ages of 3 and 5 years. The remaining two siblings and her two daughters have been in good health. Lesional skin biopsy showed vacuolated keratinocytes with abundant basophilic cytoplasm (Fig. 1b). HPV type 12, one of the EV‐related HPV types, was detected in DNA samples extracted from the scales by using the consensus primer pair, EV3 and EV4, for the polymerase chain reaction (PCR) amplification of the E7 open reading frame of EV‐associated HPVs.3 Laboratory tests showed a normal full blood count with normal white blood cell differentiation. No abnormality was found in blood chemistry tests except for an elevated level of lactate dehydrogenase (393 IU L−1, normal 120–240). The CD4/CD8 ratio of circulating lymphocytes was within normal range (1·0; normal 0·9–3·2). Values of thymidine uptake by lymphocytes stimulated with phytohaemagglutinin and concanavalin A were comparable with those of normal subjects.