Novel PPOX exonic mutation inducing aberrant splicing in a patient with homozygous variegate porphyria.

Autor: Cho SY; Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea., Lau EY; Department of Pathology, Queen Mary Hospital, Hong Kong, China., Luk DC; Paediatric & Adolescent Medical Department, United Christian Hospital, Hong Kong, China., Law CY; Department of Pathology, Queen Mary Hospital, Hong Kong, China., Lai CK; Department of Pathology, Princess Margaret Hospital, Hong Kong, China., Lam CW; Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2021 Jan; Vol. 512, pp. 117-120. Date of Electronic Publication: 2020 Nov 04.
DOI: 10.1016/j.cca.2020.10.033
Abstrakt: 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.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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