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Partial protoporphyrinogen oxidase (PPOX) gene deletions, due to different Alu-mediated mechanisms, identified by MLPA analysis in patients with variegate porphyria

Michela Barbaro12, Maire Kotajärvi23, Pauline Harper234 and Ylva Floderus2345*

Author Affiliations

1 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

2 Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden

3 Porphyria Centre Sweden, Karolinska University Hospital, Stockholm, Sweden

4 Department of Laboratory Medicine, Division of Metabolic Diseases, Karolinska Institutet, Stockholm, Sweden

5 CMMS L7:05, Karolinska University Hospital, SE-171 76, Stockholm, Sweden

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Orphanet Journal of Rare Diseases 2013, 8:13  doi:10.1186/1750-1172-8-13

Published: 16 January 2013


Variegate porphyria (VP) is an autosomal dominantly inherited hepatic porphyria. The genetic defect in the PPOX gene leads to a partial defect of protoporphyrinogen oxidase, the penultimate enzyme of heme biosynthesis. Affected individuals can develop cutaneous symptoms in sun-exposed areas of the skin and/or neuropsychiatric acute attacks. The identification of the genetic defect in VP families is of crucial importance to detect the carrier status which allows counseling to prevent potentially life threatening neurovisceral attacks, usually triggered by factors such as certain drugs, alcohol or fasting.

In a total of 31 Swedish VP families sequence analysis had identified a genetic defect in 26. In the remaining five families an extended genetic investigation was necessary. After the development of a synthetic probe set, MLPA analysis to screen for single exon deletions/duplications was performed.

We describe here, for the first time, two partial deletions within the PPOX gene detected by MLPA analysis. One deletion affects exon 5 and 6 (c.339-197_616+320del1099) and has been identified in four families, most probably after a founder effect. The other extends from exon 5 to exon 9 (c.339-350_987+229del2609) and was found in one family. We show that both deletions are mediated by Alu repeats.

Our findings emphasize the usefulness of MLPA analysis as a complement to PPOX gene sequencing analysis for comprehensive genetic diagnostics in patients with VP.

Alu-mediated deletions; Protoporphyrinogen oxidase; PPOX; VP; Variegate porphyria; MLPA