Study On Mutations Of EVER1and EVER2in Epidermodysplasia Verruciformis

Background:EV (epidermodysplasia verruciformis) is a rare genodermatosis characterized by persistent, refractory, disseminated skin lesions resembling flat warts, common warts, seborrheic keratosis or pityriasis versicolor and lesions exposed to sun are associated with a high risk of skin cancer. EV is characterized by extreme susceptibility to certain HPV (human papillomavirus) and so far various types of HPV have been detected in the lesions of EV. Studies have shown that HPV infection, genetic factors, immune factors along with environmental factors contribute to the etiology of EV. It is universally recognized that the mode of EV transmission may likely be autosomal recessive, but autosomal dominant and X-linked recessive inheritance have also been reported. Ramoz did some researches on consanguineous EV families with microsatellite markers and mapped two susceptibility locus for EV:EV1to chromosome17q25and EV2to chromosome2p21-p24. It is well known that mutations of EVER1and EVER2on chromosome17q25are closely related to the pathogenesis of EV and homozygous invalidating mutations in either gene have been found in about75%of the EV patients. So far,12kinds of functional mutations caused by a variety of mechanisms (including nonsense mutation, single nucleotide deletion, splice site mutation and exon deletion) have been isolated, seven in EVER1and five in EVER2.Purpose:Study on mutations of EVER1and EVER2to see whether there is any homozygous invalidating mutation in either gene.Methods:Collecting genomic DNA from the lesion of an EV patient. According to the information of all the exons of EVER1and EVER2supplied by UCSC Genome, design a pair of primers for each exon and amplify the DNA template. Directly sequencing the amplified DNA and analyze the sequencing results with UCSC BLAT.Results:We got the predicted segments when using the36pairs of primers to amplify the sample, the result showed a homozygous Tâ†'G mutation at nucleotide position2568within3’-UTR of EVER2,along with four SNPs (rs2748427, rs383603, rs452483, rs454138)at nucleotide position616within exon5of EVER1, nucleotide position144and196within5’-UTR of EVER2and nucleotide position2707within3’-UTR of EVER2.Conclusion:We only found a homozygous Tâ†'G mutation at nucleotide position2568within3’-UTR of EVER2and it seems not to be the pathogenic mutation of this patient. The possible reason should be:1)the mutation may locate in other functional non-coding sequences of EVER1and EVER2.2) the mutation may locate in EV2.3)the immunological deficiency take the leading role in the pathogenesis of EV in this patient.