Identification and Splicing Characterization of Novel and Variants Associated With Epidermodysplasia Verruciformis in Three Chinese Families.

: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to human beta papillomavirus infections and a particular propensity to develop non-melanoma skin cancers (NMSCs). The majority of EV cases are caused by biallelic null variants in , , and . This study aimed to identify disease-causing variants in three Chinese families with EV and to elucidate their molecular pathogenesis. : Genomic DNA from the probands of three EV families was analyzed by whole-exome sequencing (WES). cDNA sequencing was performed to investigate abnormal splicing of the variants. Quantitative RT-PCR (qRT-PCR) was conducted to quantify the mRNA expression of mutant and . : Whole-exome sequencing identified two novel homozygous variants (c.2278-2A > G in and c.559G > A in ) in families 1 and 2, respectively. In family 3, WES revealed a recurrent and a novel compound heterozygous variant, c.559G > A and c.1389G > A, in . The c.2278-2A > G variant led to the skipping of exon 19 and resulted in premature termination at codon 776. Subsequent qRT-PCR revealed that the aberrantly spliced transcript was partly degraded. Notably, the c.559G > A variant created a novel acceptor splice site at c.561 and yielded three different aberrant transcripts. qRT-PCR revealed that most of the mutant transcripts were degraded nonsense-mediated mRNA decay (NMD). : We identified three novel disease-causing variants in or in three Chinese families with EV. The EV phenotypes of the three patients were due to a reduction in TMC6 or TMC8. Our findings expand the genetic causes of EV in the Chinese population.