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Novel PPOX exonic mutation inducing aberrant splicing in a patient with homozygous variegate porphyria
- Source :
- Clinica chimica acta; international journal of clinical chemistry. 512
- Publication Year :
- 2020
-
Abstract
- Introduction Variegate porphyria (VP; OMIM 176200) is one of the acute hepatic porphyrias, and it is characterized by the partial deficiency of protoporphyrinogen oxidase (PPOX). The unusual homozygous variant with mutations on both alleles of PPOX is distinguished with general heterozygous VP by several typical points such as severe defect in PPOX enzyme activity, early onset of photosensitivity before puberty, and skeletal deformity. Material and method In this study, we describe a very rare case of autosomal recessive form of true homozygous VP found in a Chinese patient with consanguineous parents. Sanger sequencing of the PPOX gene showed a novel homozygous variant located at the first base of exon 8 of the gene, i.e., NM_000309.3c.808G > T. To investigate aberrant splicing induced by the mutant, wild-type exon 8 and mutant exon 8 were expressed in pET01 vector as minigene in cultured-cells and analyzed by RT-PCR. Results The wildtype PPOX showed an expected band in the gel electrophoresis after RT-PCR. The PPOX c.808G > T only showed a band similar to the band size of the vector only control. This result suggested c.808G > T mutant is an exonic mutation inducing aberrant splicing of pre-mRNA of the PPOX gene. Conclusion This study showed a very rare case of homozygous VP with autosomal recessive homoallelic pattern. In comparison with previous cases of homozygous VP presenting brachydactyly, it is notable that our patient did not have any skeletal deformities.
- Subjects :
- 0301 basic medicine
Variegate porphyria
Clinical Biochemistry
Mutant
Biology
Biochemistry
Mitochondrial Proteins
03 medical and health sciences
Exon
symbols.namesake
0302 clinical medicine
medicine
Humans
Protoporphyrinogen Oxidase
Allele
Sanger sequencing
Genetics
Flavoproteins
Biochemistry (medical)
Brachydactyly
General Medicine
Exons
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
Mutation
symbols
Protoporphyrinogen oxidase
Porphyria, Variegate
Minigene
Subjects
Details
- ISSN :
- 18733492
- Volume :
- 512
- Database :
- OpenAIRE
- Journal :
- Clinica chimica acta; international journal of clinical chemistry
- Accession number :
- edsair.doi.dedup.....6e128ebf4759234c37cd3da472f0b8aa