{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:59:22Z","timestamp":1785898762162,"version":"3.56.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T00:00:00Z","timestamp":1213920000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genet"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A partial deficiency in Protoporphyrinogen oxidase (PPOX) produces the mixed disorder Variegate Porphyria (VP), the second acute porphyria more frequent in Argentina. Identification of patients with an overt VP is absolutely important because treatment depends on an accurate diagnosis but more critical is the identification of asymptomatic relatives to avoid acute attacks which may progress to death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have studied at molecular level 18 new Argentinean patients biochemically diagnosed as VP. PPOX gene was amplified in one or in twelve PCR reactions. All coding exons, flanking intronic and promoter regions were manual or automatically sequenced. For RT-PCR studies RNA was retrotranscripted, amplified and sequenced. PPOX activity in those families carrying a new and uncharacterized mutation was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All affected individuals harboured mutations in heterozygous state. Nine novel mutations and 3 already reported mutations were identified. Six of the novel mutations were single nucleotide substitutions, 2 were small deletions and one a small insertion. Three single nucleotide substitutions and the insertion were at exon-intron boundaries. Two of the single nucleotide substitutions, c.471G&gt;A and c.807G&gt;A and the insertion (c.388+3insT) were close to the splice donor sites in exons 5, 7 and intron 4 respectively. The other single nucleotide substitution was a transversion in the last base of intron 7, g.3912G&gt;C (c.808-1G&gt;C) so altering the consensus acceptor splice site. However, only in the first case the abnormal band showing the skipping of exon 5 was detected. The other single nucleotide substitutions were transversions: c.101A&gt;T, c.995G&gt;C and c.670 T&gt;G that result in p.E34V, p.G332A and W224G aminoacid substitutions in exons 3, 10 and 7 respectively. Activity measurements indicate that these mutations reduced about 50% PPOX activity and also that they co-segregate with this reduced activity value. Two frameshift mutations, c.133delT and c.925delA, were detected in exons 3 and 9 respectively. The first leads to an early termination signal 22 codons downstream (p.S45fsX67) and the second leads to a stop codon 5 codons downstream (p.I309fsX314). One reported mutation was a missense mutation (p.G232R) and 2 were frameshift mutations: c.1082insC and 1043insT. The last mutation was detected in six new apparently unrelated Argentinean families.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Molecular analysis in available family members revealed 14 individuals who were silent carriers of VP. Molecular techniques represent the most accurate approach to identify unaffected carriers and to provide accurate genetic counselling for asymptomatic individuals. The initial screening includes the insertion search.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2350-9-54","type":"journal-article","created":{"date-parts":[[2008,6,21]],"date-time":"2008-06-21T06:13:15Z","timestamp":1214028795000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genetic and biochemical studies in Argentinean patients with variegate porphyria"],"prefix":"10.1186","volume":"9","author":[{"given":"Mar\u00eda V","family":"Rossetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara X","family":"Granata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Giudice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E","family":"Parera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alcira","family":"Batlle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,6,20]]},"reference":[{"issue":"14","key":"348_CR1","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1056\/NEJM198004033021401","volume":"302","author":"DA Brenner","year":"1980","unstructured":"Brenner DA, Bloommer JR: The enzymatic defect in variegate Porphyria. Studies with human cultured skin fibroblasts. N Engl J Med. 1980, 302 (14): 765-769.","journal-title":"N Engl J Med"},{"key":"348_CR2","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/BF00282829","volume":"58","author":"JC Deybach","year":"1981","unstructured":"Deybach JC, de Verneuil H, Nordmann Y: The inherited enzymatic defect in Porphyria variegata. Hum Genet. 1981, 58: 425-428. 10.1007\/BF00282829.","journal-title":"Hum Genet"},{"key":"348_CR3","first-page":"1435","volume-title":"Dermatology in General Medicine","author":"DR Bickers","year":"2003","unstructured":"Bickers DR, Frank J: The porphyrias. Dermatology in General Medicine. Edited by: Fitzpatrick TB, Freedkey IM, Eisen AZ, Wolff K, Freedberg IM, Austen KF, Goldsmith LA, Katz ST. 2003, New York: Mc Graw \u2013 Hill, 1435-1466. 6","edition":"6"},{"key":"348_CR4","volume-title":"Porfirinas y Porfirias. Aspectos cl\u00ednicos, bioqu\u00edmicos y biolog\u00eda molecular. Actualizaciones m\u00e9dico-bioqu\u00edmicas","author":"AMC Batlle","year":"1997","unstructured":"Batlle AMC: Porfirinas y Porfirias. Aspectos cl\u00ednicos, bioqu\u00edmicos y biolog\u00eda molecular. Actualizaciones m\u00e9dico-bioqu\u00edmicas. Edited by: Acta Bioqu\u00edmica Cl\u00ednica Latinoamericana. 1997, Federaci\u00f3n Bioqu\u00edmica de la Provincia de Buenos Aires"},{"key":"348_CR5","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"KE Anderson","year":"2001","unstructured":"Anderson KE, Sassa S, Bishop D, Desnick R: The Porphyrias. The Metabolic and Molecular Basis of Inherited Disease. Edited by: Scriver CR, Beaudet AL, Sly WS, Valle D. 2001, New York: McGraw-Hill, 8","edition":"8"},{"key":"348_CR6","first-page":"88","volume":"13","author":"J Frank","year":"1997","unstructured":"Frank J, Christiano AM: Genetic research strategies: A review of the acute porphyrias. Retinoids. 1997, 13: 88-92.","journal-title":"Retinoids"},{"key":"348_CR7","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1159\/000056373","volume":"14","author":"P Poblete-Guti\u00e9rrez","year":"2001","unstructured":"Poblete-Guti\u00e9rrez P, M\u00e9ndez M, Wiederholt T, Merk HF, Fontanellas A, Wolff C, Frank J: Diagnosis and Treatment of the acute porphyrias: an interdisciplinary challenge. Skin Pharmacol Appl Skin Physiol. 2001, 14: 393-400. 10.1159\/000056373.","journal-title":"Skin Pharmacol Appl Skin Physiol"},{"key":"348_CR8","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1111\/j.1365-2133.2005.06978.x","volume":"154","author":"P Poblete Guti\u00e9rrez","year":"2005","unstructured":"Poblete Guti\u00e9rrez P, Wolff C, Far\u00edas R, Frank J: A Chilean boy with severe photosensitivity and finger shortening: the first case of homozygous variegate porphyria in South America. Br J Dermatol. 2005, 154: 368-371. 10.1111\/j.1365-2133.2005.06978.x.","journal-title":"Br J Dermatol"},{"key":"348_CR9","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S0140-6736(84)92298-0","volume":"1","author":"V Kordac","year":"1984","unstructured":"Kordac V, Deybach JC, Martasek P, Zeman J, da Silva V, Nordmann Y, Houstkova H, Rubin A, Holub J: Homozygous variegate porphyria. Lancet. 1984, 1: 851-10.1016\/S0140-6736(84)92298-0.","journal-title":"Lancet"},{"key":"348_CR10","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1136\/pgmj.69.816.781","volume":"69","author":"RJ Hift","year":"1993","unstructured":"Hift RJ, Meissner PN, Todd G, Kirby P, Bilsland D, Collins P, Ferguson J, Moore MR: Homozygous variegate porphyria: an evolving clinical syndrome. Postgrad Med J. 1993, 69: 781-786.","journal-title":"Postgrad Med J"},{"key":"348_CR11","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1093\/hmg\/7.12.1921","volume":"7","author":"AG Roberts","year":"1998","unstructured":"Roberts AG, Puy H, Dailey TA: Molecular characterization of homozygous variegate porphyria. Hum Mol Genet. 1998, 7: 1921-1925. 10.1093\/hmg\/7.12.1921.","journal-title":"Hum Mol Genet"},{"key":"348_CR12","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1046\/j.1523-1747.1998.00148.x","volume":"110","author":"J Frank","year":"1998","unstructured":"Frank J, McGrath J, Lam H, Graham RM, Hawk JLM, Christiano AM: Homozygous variegate porphyria: identification of mutations on both alleles of the protoporphyrinogen oxidase gene in a severely affected probands. J Invest Dermatol. 1998, 110: 452-455. 10.1046\/j.1523-1747.1998.00148.x.","journal-title":"J Invest Dermatol"},{"key":"348_CR13","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1006\/mgme.2000.2975","volume":"69","author":"AV Corrigall","year":"2000","unstructured":"Corrigall AV, Hift RJ, Davids LM, Hancock V, Meissner D, Kirsch RE, Meissner PN: Homozygous Variegate Porphyria in South Africa: Genotypic Analysis in Two Cases. Mol Genet Metab. 2000, 69: 323-330. 10.1006\/mgme.2000.2975.","journal-title":"Mol Genet Metab"},{"key":"348_CR14","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1046\/j.1523-1747.2001.01293.x","volume":"116","author":"R Kauppinen","year":"2001","unstructured":"Kauppinen R, Timonen K, von und zu Fraunberg M, Laitinene E, Ahola H, Tenhunen R, Taketani S, Mustajoki P: Homozygous variegate Porphyria: 20 years follow-up and characterization of molecular defect. J Invest Dermatol. 2001, 116: 610-613. 10.1046\/j.1523-1747.2001.01293.x.","journal-title":"J Invest Dermatol"},{"key":"348_CR15","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1046\/j.1365-2133.2001.04147.x","volume":"144","author":"RA Palmer","year":"2001","unstructured":"Palmer RA, Elder GH, Barrett DF, Keohane SG: Homozygous variegate Porphyria: a compound heterozygote with novel mutations in the protoporphyrinogen oxidase gene. Br J Dermatol. 2001, 144: 866-869. 10.1046\/j.1365-2133.2001.04147.x.","journal-title":"Br J Dermatol"},{"key":"348_CR16","first-page":"230","volume":"16","author":"P Poblete-Guti\u00e9rrez","year":"2006","unstructured":"Poblete-Guti\u00e9rrez P, Wiederholt T, Merk HF, Frank J: The Porphyrias: clinical presentation, diagnosis and treatment. Eur J Dermatol. 2006, 16: 230-240.","journal-title":"Eur J Dermatol"},{"key":"348_CR17","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1373\/clinchem.2003.025213","volume":"50","author":"RJ Hift","year":"2004","unstructured":"Hift RJ, Davidson BP, Hooft van Der C, Meissner DM, Meissner PN: Plasma Fluorescence Scanning and Fecal Porphyrin Analysis for the Diagnosis of Variegate Porphyria: Precise Determination of Sensitivity and Specificity with Detection of Protoporphyrinogen Oxidase Mutations as a Reference Standard. Clinical Chemistry. 2004, 50: 915-923. 10.1373\/clinchem.2003.025213.","journal-title":"Clinical Chemistry"},{"key":"348_CR18","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1006\/geno.1995.9949","volume":"29","author":"S Taketani","year":"1995","unstructured":"Taketani S, Inazawa J, Abe T, Furukawa T, Kohno H, Tokunaga R, Nishimura K, Inokuchi H: The human protoporphyrinogen oxidase (PPOX) gene: organization and location to chromosome 1. Genomics. 1995, 29: 698-703. 10.1006\/geno.1995.9949.","journal-title":"Genomics"},{"key":"348_CR19","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1093\/hmg\/4.12.2387","volume":"4","author":"AG Roberts","year":"1995","unstructured":"Roberts AG, Whatley SH, Daniels J, Holmans P, Fenton I, Owen MJ, Thompson P, Long C, Elder GH: Partial characterization and assignment of the gene for protoporphyrinogen oxidase and variegate porphyria to human chromosome 1q23. Hum Mol Genet. 1995, 4: 2387-2390. 10.1093\/hmg\/4.12.2387.","journal-title":"Hum Mol Genet"},{"key":"348_CR20","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1006\/bbrc.1996.1337","volume":"226","author":"H Puy","year":"1996","unstructured":"Puy H, Robreau AM, Rosipal R, Nordmann Y, Deybach JC: Protoporphyrinogen oxidase: complete genomic sequence and polymorphisms in the human gene. Biochem Biophys Res Commun. 1996, 226: 226-230. 10.1006\/bbrc.1996.1337.","journal-title":"Biochem Biophys Res Commun"},{"key":"348_CR21","doi-asserted-by":"publisher","first-page":"8076","DOI":"10.1074\/jbc.270.14.8076","volume":"270","author":"K Nishimura","year":"1995","unstructured":"Nishimura K, Taketani S, Inokuchi H: Cloning of a human cDNA for protoporphyrinogen oxidase by complementation in vivo of a hemG mutant of Escherichia coli. J Biol Chem. 1995, 270: 8076-8080. 10.1074\/jbc.270.14.8076.","journal-title":"J Biol Chem"},{"key":"348_CR22","unstructured":"Human Gene Mutation Database. [http:\/\/www.hgmd.cf.ac.uk\/ac\/index.php]"},{"key":"348_CR23","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1086\/301833","volume":"62","author":"JZ Groenewald","year":"1998","unstructured":"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 Genet. 1998, 62: 1254-1258. 10.1086\/301833.","journal-title":"Am J Genet"},{"key":"348_CR24","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/ng0596-95","volume":"13","author":"PN Meissner","year":"1996","unstructured":"Meissner PN, Dailey TA, Hift RJ, Ziman M, Corrigall AV, Roberts AG, Meissner DM, Kircsh RE, Dailey RA: 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. 10.1038\/ng0596-95.","journal-title":"Nat Genet"},{"key":"348_CR25","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1093\/hmg\/5.7.981","volume":"5","author":"L Warnich","year":"1996","unstructured":"Warnich L, Kotze MJ, Groenewald IM, Groenewald JZ, van Brakel MG, van Heerden CJ, de Villiers JN, Ven van de WJ, Schoenmakers EF, Taketani S, Retief AE: Identification of three mutattions and associated haplotypes in the protoporphyrinogen oxidase gene in South African families with Variegate porphyria. Hum Mol Genet. 1996, 5: 981-984. 10.1093\/hmg\/5.7.981.","journal-title":"Hum Mol Genet"},{"key":"348_CR26","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.0906-6705.2005.00228.x","volume":"14","author":"PIN De Villiers","year":"2005","unstructured":"De Villiers PIN, Kotze MJ, Van Heerden CJ, Sadie A, Gardner HFJ, 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. Ex Dermatol. 2005, 14: 50-55. 10.1111\/j.0906-6705.2005.00228.x.","journal-title":"Ex Dermatol"},{"key":"348_CR27","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1159\/000053337","volume":"51","author":"J Frank","year":"2001","unstructured":"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. 10.1159\/000053337.","journal-title":"Hum Hered"},{"key":"348_CR28","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/1098-1004(200007)16:1<96::AID-HUMU34>3.0.CO;2-P","volume":"16","author":"A De Siervi","year":"2000","unstructured":"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. 10.1002\/1098-1004(200007)16:1<96::AID-HUMU34>3.0.CO;2-P.","journal-title":"Hum Mut"},{"key":"348_CR29","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/1098-1004(200012)16:6<532::AID-HUMU18>3.0.CO;2-S","volume":"16","author":"A De Siervi","year":"2000","unstructured":"De Siervi A, Parera VE, Batlle A, Rossetti MV: Two new mutations (H106P and L178V) in the protoporphyrinogen oxidase gene in Argentinean patients with variegate porphyria. Hum Mut. 2000, 16: 532-534. 10.1002\/1098-1004(200012)16:6<532::AID-HUMU18>3.0.CO;2-S.","journal-title":"Hum Mut"},{"key":"348_CR30","first-page":"493","volume":"49","author":"VE Parera","year":"2003","unstructured":"Parera VE, De Siervi A, Varela LS, Rossetti MV, Batlle A: Acute Porphyrias in the Argentinean population. A review. Cell Mol Biol. 2003, 49: 493-500.","journal-title":"Cell Mol Biol"},{"key":"348_CR31","first-page":"145","volume-title":"Porfirinas y Porfirias. Aspectos cl\u00ednicos, bioqu\u00edmicos y biolog\u00eda molecular. Actualizaciones m\u00e9dico-bioqu\u00edmicas","author":"AMC Batlle","year":"1997","unstructured":"Batlle AMC: El laboratorio de las Porfirias. Porfirinas y Porfirias. Aspectos cl\u00ednicos, bioqu\u00edmicos y biolog\u00eda molecular. Actualizaciones m\u00e9dico-bioqu\u00edmicas. Edited by: Acta Bioqu\u00edmica Cl\u00ednica Latinoamericana. 1997, Federaci\u00f3n Bioqu\u00edmica de la Provincia de Buenos Aires, 145-171."},{"key":"348_CR32","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/sj.emboj.7600189","volume":"23","author":"M Koch","year":"2004","unstructured":"Koch M, Breithaup C, Kiefersauer R, Freigang J, Huber R, Messeschmidt A: Crystal structure of protoporphyrinogen IX oxidase: a key enzyme in haem and chorophyll biosynthesis. The Embo Journal. 2004, 23: 1720-1728. 10.1038\/sj.emboj.7600189.","journal-title":"The Embo Journal"},{"key":"348_CR33","unstructured":"Swiss PDB Viewer. [http:\/\/www.rcsb.org\/pdb\/home\/home.do]"},{"key":"348_CR34","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/0378-1119(94)90567-3","volume":"141","author":"K Nakai","year":"1994","unstructured":"Nakai K, Sakamoto H: Construction of a novel database containing aberrant splicing mutations of mammalian genes. Gene. 1994, 141: 171-177. 10.1016\/0378-1119(94)90567-3.","journal-title":"Gene"},{"key":"348_CR35","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1093\/hmg\/5.3.407","volume":"5","author":"JC Deybach","year":"1996","unstructured":"Deybach JC, Puy H, Robreau AM, Lamoril J, Da Silva V, Grandchamp B, Nordmann Y: Mutations in the protoporphyrinogen oxidase gene in patients with variegate porphyria. Hum Mol Genet. 1996, 5: 407-410. 10.1093\/hmg\/5.3.407.","journal-title":"Hum Mol Genet"},{"key":"348_CR36","first-page":"596","volume-title":"Human Mutation Mutation in Brief","author":"M D'Amato","year":"2003","unstructured":"D'Amato M, Bonuglia M, Barile S, Griso D, Macri A, Biolcati G: Genetic Analysis of Variegate Porphyria (VP) in Italy: Identification of six novel mutations in the Protoporphyrinogen oxidase (PPOX) Gene. Human Mutation Mutation in Brief. 2003, 596-"},{"key":"348_CR37","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1086\/302586","volume":"65","author":"SD Whatley","year":"1999","unstructured":"Whatley SD, Puy H, Morgan RR, Robreau AM, Roberts AG, Nordmann Y, Elder GH, Deybach JC: Variegate Porphyria in Western Europe: identification of PPOX gene mutations in 104 families, extent of allelic heterogeneity, and absence of correlation between phenotype and type of mutation. Am J Hum Genet. 1999, 65: 984-994. 10.1086\/302586.","journal-title":"Am J Hum Genet"},{"key":"348_CR38","first-page":"515","volume":"136","author":"X Schneider-Yin","year":"2006","unstructured":"Schneider-Yin X, Minder EI: Swiss patients with variegate porphyria have unique mutations. Swiss Med Wkly. 2006, 136: 515-519.","journal-title":"Swiss Med Wkly"},{"issue":"8","key":"348_CR39","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/j.1468-3083.2006.01705.x","volume":"20","author":"M Lecha","year":"2006","unstructured":"Lecha M, Baddenas C, Puig S, Orfila J, Mila M, To-Figueras J, Mu\u00f1oz C, Mercader P, Herrero C: Genetic studies in variegate porphyria in Spain. Identification of gene mutations and family study for carrier detection. J Eur Acad Dermatol Venereol. 2006, 20 (8): 974-979.","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"348_CR40","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/sj.ejhg.5200860","volume":"10","author":"M von und zu Fraunberg","year":"2002","unstructured":"von und zu Fraunberg M, Timonen K, Mustajoki P, Kauppinen R: Clinical and biochemical characteristics and genotype-phenotype correlation in Finnish variegate porphyria patients. Eur J Hum Genet. 2002, 10: 649-657. 10.1038\/sj.ejhg.5200860.","journal-title":"Eur J Hum Genet"},{"key":"348_CR41","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/0020-711X(80)90173-1","volume":"12","author":"L Eales","year":"1980","unstructured":"Eales L, Day RS, Blekkenhorst : The clinical and biochemical features of variegate porphyria: an analysis of 300 cases at Groote Schuur Hospital, Cape Town. Int J Biochem. 1980, 12: 837-853. 10.1016\/0020-711X(80)90173-1.","journal-title":"Int J Biochem"},{"key":"348_CR42","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1111\/j.1365-2133.2004.06120.x","volume":"151","author":"RJ Hift","year":"2004","unstructured":"Hift RJ, Meissner D, Meissner PN: Presystematic study of the clinical and biochemical expression of variegate Porphyria in a large South African family. Br J Dermatol. 2004, 151: 465-471. 10.1111\/j.1365-2133.2004.06120.x.","journal-title":"Br J Dermatol"},{"key":"348_CR43","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1128\/MCB.15.2.809","volume":"15","author":"SW Peltz","year":"1995","unstructured":"Peltz SW, Feng R, Weich A, Jacobson A: Non sense-mediated mRNA decay in yeast. Mol Cell Biol. 1995, 15: 809-823.","journal-title":"Mol Cell Biol"},{"key":"348_CR44","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0378-1119(01)00552-2","volume":"274","author":"CI Gonz\u00e1lez","year":"2004","unstructured":"Gonz\u00e1lez CI, Bhattacharya A, Wang W, Peltz SW: Non sense-mediated mRNA decay in Saccharomyces cerevisie. Gene. 2004, 274: 15-25. 10.1016\/S0378-1119(01)00552-2.","journal-title":"Gene"},{"key":"348_CR45","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.1128\/MCB.17.4.2143","volume":"17","author":"LR Coultier","year":"1997","unstructured":"Coultier LR, Landree MA, Cooper TA: Identification of a new class of exonic splicing enhancers by in vivo selection. Mol Cell Biol. 1997, 17: 2143-2150.","journal-title":"Mol Cell Biol"},{"key":"348_CR46","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1128\/MCB.19.3.1705","volume":"19","author":"TD Schaal","year":"1999","unstructured":"Schaal TD, Maniatis T: Selection and characterization of pre-mRNA splicing enhancers: Identification of novel SR protein-specific enhancer sequences. Mol Cell Biol. 1999, 19: 1705-1719.","journal-title":"Mol Cell Biol"},{"key":"348_CR47","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nrg775","volume":"3","author":"CL Cartegani","year":"2002","unstructured":"Cartegani CL, Chew SL, Krainer AR: Listening to silence and Understanding nonsense: exonic mutations that affect splicing. Nature Rewiews. 2002, 3: 285-298. 10.1038\/nrg775.","journal-title":"Nature Rewiews"},{"key":"348_CR48","doi-asserted-by":"publisher","first-page":"15700","DOI":"10.1073\/pnas.0404901101","volume":"101","author":"G Yeo","year":"2004","unstructured":"Yeo G, Hoon S, Venkatech B, Buege CB: Variation in sequence and organization of splicing regulatory elements in vertebrate genes. Proc Natl Acad Sci. 2004, 101: 15700-15705. 10.1073\/pnas.0404901101.","journal-title":"Proc Natl Acad Sci"},{"key":"348_CR49","doi-asserted-by":"crossref","unstructured":"Fairbrother WG, Yeo GW, Yeh R, Goldstein P, Mawson M, Sharp PA, Burge CB: RESCUE-ESE identifies candidate exonic splicing enhancers in-ertebrate exons. Nucleic Acids Research. 2004, W187-W190. 10.1093\/nar\/gkh393. 32 Web Server","DOI":"10.1093\/nar\/gkh393"},{"key":"348_CR50","doi-asserted-by":"publisher","first-page":"13376","DOI":"10.1074\/jbc.M300151200","volume":"278","author":"M von und zu Fraunberg","year":"2003","unstructured":"von und zu Fraunberg M, Nyronen KT, Kaupinnen R: Mitochondrial targeting of normal and mutant protoporphyrinogen oxidase. J Biol Chem. 2003, 278: 13376-81. 10.1074\/jbc.M300151200.","journal-title":"J Biol Chem"},{"key":"348_CR51","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1042\/bj20030978","volume":"377","author":"RP Morgan","year":"2004","unstructured":"Morgan RP, Errington R, Elder GH: Identification of sequences required for the import of human protoporphyrinogen oxidase to mitochondria. Biochem J. 2004, 377: 281-7. 10.1042\/BJ20030978.","journal-title":"Biochem J"},{"key":"348_CR52","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.cellbi.2006.02.001","volume":"30","author":"L Davids","year":"2006","unstructured":"Davids L, Corrigall AV, Meissner PN: Mitochondrial targeting of human protoporphyrinogen oxidase. Cell Biology International. 2006, 30: 416-426. 10.1016\/j.cellbi.2006.02.001.","journal-title":"Cell Biology International"},{"key":"348_CR53","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1034\/j.1399-0004.2003.00116.x","volume":"64","author":"A Wiman","year":"2003","unstructured":"Wiman A, Harper P, Floderus Y: Nine novel mutations in the protoporphyrinogen oxidase in Swedish families with variegate porphyria. Clin Genet. 2003, 64: 122-130. 10.1034\/j.1399-0004.2003.00116.x.","journal-title":"Clin Genet"}],"container-title":["BMC Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-9-54.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2350-9-54\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-9-54","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2350-9-54.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T18:22:32Z","timestamp":1709058152000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenet.biomedcentral.com\/articles\/10.1186\/1471-2350-9-54"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,20]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["348"],"URL":"https:\/\/doi.org\/10.1186\/1471-2350-9-54","relation":{},"ISSN":["1471-2350"],"issn-type":[{"value":"1471-2350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,20]]},"assertion":[{"value":"19 July 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"54"}}