Background/Aims: The porphyrias are genetically heterogeneous diseases, and each mutation is exclusive to one or two families. Among the mutations responsible for variegate porphyria in our country, c.1042_1043insT stands out, since it was described only in Argentina and is present in about 40% of genetically diagnosed families. Thus, we hypothesized the possible existence of a common ancestor for the mutation in our population. Methods: We conducted a study based on microsatellite (short tandem repeats) haplotypes. Results: We found a common haplotype in all of the patients carrying the common mutation. The age of the mutation was estimated to be about 375 years. Conclusion: There is a recent founder effect in our population for this particular genetic alteration in variegate porphyria.

1.
Méndez M, Granata BX, Jiménez MJ, Parera VE, Batlle A, de Salamanca RE, Rossetti MV: Functional characterization of five protoporphyrinogen oxidase missense mutations found in Argentinean variegate porphyria patients. JIMD Rep 2012;4:91-97.
2.
Puy H, Gouya L, Deybach JC: Porphyrias. Lancet 2010;13:375, 924-937.
3.
Meissner PN, Dailey TA, Hift RJ, Ziman M, Corrigall AV, Roberts AG, Meissner DM, Kirsch RE, Dailey HA: A R59W mutation in human protoporphyrinogen oxidase results in decreased enzyme activity and is prevalent in South Africans with variegate porphyria. Nat Genet 1996;13:95-97.
4.
De Rooij FWM, Minderman G, de Barr C: Six new protoporphyrinogen oxidase mutations in Dutch variegate porphyria patients and the R59W mutation in historical perspective. Acta Haematol 1997;98(suppl 1):103.
5.
Groenewald JZ, Liebenberg J, Groenewald IM, Warnich L: Linkage disequilibrium analysis in a recently founded population: evaluation of the variegate porphyria founder in South African Afrikaners. Am J Hum Genet 1998;62:1254-1258.
6.
de Villiers JN, Kotze MJ, van Heerden CJ, Sadie A, Gardner HF, Liebenberg J, van Zyl R, du Plessis L, Kimberg M, Frank J, Warnich L: Overrepresentation of the founder PPOX gene mutation R59W in a South African patient with severe clinical manifestation of porphyria. Exp Dermatol 2005;14:50-55.
7.
van Tuyll Van Serooskerke AM, Schneider-Yin X, Schimmel RJ, Bladergroen RS, Poblete-Gutiérrez P, Barman J, van Geel M, Frank J, Minder EI: Identification of a recurrent mutation in the protoporphyrinogen oxidase gene in Swiss patients with variegate porphyria: clinical and genetic implications. Cell Mol Biol (Noisy-le-grand) 2009;55:96-101.
8.
van Tuyll van Serooskerken AM, Drögemöller BI, Te Velde K, Bladergroen RS, Steijlen PM, Poblete-Gutiérrez P, van Geel M, van Heerden CJ, Warnich L, Frank J: Extended haplotype studies in South African and Dutch variegate porphyria families carrying the recurrent p.R59W mutation confirm a common ancestry. Br J Dermatol 2012;166:261-265.
9.
Frank J, Aita VM, Ahmad W, Lam H, Wolff C, Christiano AM: Identification of a founder mutation in the protoporphyrinogen oxidase gene in variegate porphyria patients from Chile. Hum Hered 2001;51:160-168.
10.
De Siervi A, Parera VE, Varela LS, Batlle A, Rossetti MV: A novel mutation (1320InsT) identified in two Argentine families with Variegate Porphyria. Hum Mut 2000;16:96-98.
11.
Oetting WS, Lee HK, Flanders DJ, Wiesner GL, Sellers TA, King RA: Linkage analysis with multiplexed short tandem repeat polymorphisms using infrared fluorescence and M13 tailed primers. Genomics 1995;30:450-458.
12.
Schuelke M: An economic method for the fluorescent labeling of PCR fragments. Nat Biotechnol 2000;18:233-234.
13.
Boutin-Ganache I, Raposo M, Raymond M, Deschepper CF: M13 - tailed primers improve the readability and usability of microsatellite analyses performed with two different allele-sizing methods. Biotechniques 2001;31:24-28.
14.
Genin E, Tulio-Pelet A, Begeat F, Lyonnet S, Abel L: Estimating the age of rare disease mutations: the example of Triple-A-syndrome. J Med Genet 2004;41:445-449.
15.
Schneider-Yin X, Hergersberg M, Goldgar DE, Rüfenacht UB, Schuurmans MM, Puy H, Deybach JC, Minder EI: Ancestral founder of mutation W283X in the porphobilinogen deaminase gene among acute intermittent porphyria patients. Hum Hered 2002;54:69-81.
16.
Granata BX, Marques Serra P, Parera VE, Batlle A, Rossetti MV: Análisis de haplotipos en pacientes Argentinos con porfiria variegata. Medicina 2008;68(suppl II):181.
17.
Schneider-Yin X, Minder EI: Swiss patients with variegate porphyria have unique mutations. Swiss Med Wkly 2006;136:515-519.
18.
Avena SA, Goicochea AS, Rey J, Dugoujon JM, Dejean CB, Carnese FR: Mezcla génica en una muestra poblacional de la ciudad de Buenos Aires. Medicina (Buenos Aires) 2006;66:113-118.
19.
Corach D, Lao O, Bobillo C, van Der Gaag K, Zuniga S, Vermeulen M, van Duijn K, Goedbloed M, Vallone PM, Parson W, de Knijff P, Kayser M: Inferring continental ancestry of Argentineans from autosomal, Y-chromosomal and mitochondrial DNA. Ann Hum Genet 2010;74:65-76.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.