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

Orphanet Journal of Rare Diseases

Ylva Floderus⁴  Pauline Harper¹  Maire Kotajärvi³  Michela Barbaro² 

[1] Department of Laboratory Medicine, Division of Metabolic Diseases, Karolinska Institutet, Stockholm, Sweden;Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden;Porphyria Centre Sweden, Karolinska University Hospital, Stockholm, Sweden;CMMS L7:05, Karolinska University Hospital, SE-171 76, Stockholm, Sweden

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

Others  :  864138
DOI  :  10.1186/1750-1172-8-13

 received in 2012-08-28, accepted in 2013-01-09,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Barbaro et al.; licensee BioMed Central Ltd.

【 图 表 】

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