Novel PPOX mutations in two variegate porphyria pedigrees

Abstract

Abstract Objective Variegate porphyria (VP) is an autosomal dominant inherited disease caused by mutation of the PPOX gene and impacted activity of the protoporphyrinogen oxidase (PPOX). We report two pedigrees of young women who present VP-related manifestation such as blistering, flushing, scarring, and hyperpigmentation after sunlight exposure. The genetic analysis of PPOX gene was performed. Methods Whole exome sequencing was conducted for both probands, followed by poly chain reaction (PCR) to amplify interested region and validate the suspicious mutations. Reverse transcriptive PCR was conducted to explore the impact of intronic mutation on the splicing process. Results The genetic analysis revealed two novel mutations: c.82_83delCC:p.Pro28* and c.222 + 2delT in heterozygous state. The first mutation leads to a premature termination of PPOX translation and the second one causes the insertion of intron2 between exon2 and exon3. Both of the probands inherit PPOX mutation from their healthy father. Conclusions Our study provides molecular diagnosis for two VP pedigrees and identified two novel PPOX mutations. We propose a hypothesis that the incomplete penetrance of VP in these two cases might be associated with sexuality and hormone level.