Three novel mutations in the protoporphyrinogen oxidase gene in Japanese patients with variegate porphyria

Maeda, Naoto; Horie, Yutaka; Sasaki, Yoko; Adachi, Kaori; Nanba, Eiji; Nishida, Kenji; Saigo, Ryuji; Nakagawa, Masanori; Kawasaki, Hironaka; Kudo, Yoshiro; Kondo, Masao

doi:10.1016/s0009-9120(00)00142-9

Cited by 6 publications

(2 citation statements)

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“…The 5.5‐kb gene encoding the 477‐amino acid PPOX enzyme is located on chromosome 1q22‐23 and contains one non‐coding and 12 coding exons (5–8). Several mutations in this gene have been identified and coupled to VP (9–20, and the Human Gene Mutation Database).…”

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confidence: 99%

Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria

2003

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Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. Protoporphyrinogen oxidase catalyses the penultimate step of haem biosynthesis, and mutations in the PPOX gene have been coupled to VP. In the present study, sequencing analysis revealed 10 different mutations in the PPOX gene in 14 out of 17 apparently unrelated Swedish VP families. Six of the identified mutations, 3G > A (exon 2), 454C > T (exon 5), 472G > C (exon 6), 614C > T (exon 6), 988G > C (exon 10) and IVS12 + 2T > G (intron 12), are single nucleotide substitutions, while 604delC (exon 6), 916-17delCT (exon 9) and 1330-31delCT (exon 13) are small deletions, and IVS12 + 2-3insT (intron 12) is a small insertion. Only one of these 10 mutations has been reported previously. Three of the mutations were each identified in two or more families, while the remaining mutations were specific for an individual family. In addition to the 10 mutations, one previously unreported single nucleotide polymorphism was identified. Mutation analysis of family members revealed two adults and four children who were silent carriers of the VP trait. Genetic analysis can now be added to the conventional biochemical analyses and used in investigation of putative carriers of a VP trait in these families.

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Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria

2003

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“…PPOX spans approximately 5 Kb of genomic DNA, and contains 1 non coding and 12 coding exons (Taketani et al, 1995;Puy et al, 1996). To date, sequencing of the gene in VP patients has revealed more than 80 mutations Meissner et al, 1996;Warnich et al, 1996;Lam et al, 1997;Corrigall et al, 1998;Frank et al, 1998a;Frank et al, 1998b;Frank et al, 1998c;Roberts et al, 1998;Whatley et al, 1999;De Siervi et al, 2000;Maeda et al, 2000;Siervi et al, 2000;Frank et al, 2001a;Frank et al, 2001b;Palmer et al, 2001;von und zu Fraunberg et al, 2001). Despite a largely overlapping clinical phenotype, Variegate Porphyria is genetically characterized by a high level of heterogeneity: insertions, deletions, splicing defects, missense, and nonsense mutations have all been reported, and are virtually spread over the entire coding region of the gene.…”

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confidence: 99%

Genetic analysis of Variegate Porphyria (VP) in Italy: Identification of six novel mutations in the protoporphyrinogen oxidase (PPOX) gene

et al. 2003

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Variegate Porphyria (VP) is one of the acute hepatic porphyrias, and is clinically characterised by skin lesions and acute neuropsychiatric/visceral attacks that occur separately or together. The disorder is caused by a partial deficiency of protoporphyrinogen oxidase, the penultimate enzyme in the heme biosynthetic pathway, and a number of mutations have been described for the corresponding gene (PPOX). Here we report a genetic analysis of VP in Italy, and the identification of six novel and three previously characterised mutations from nine affected individuals and families. Among those newly identified, two mutations were small deletions (c.418_419delAA; c.759delA), leading to the formation of premature stop codons, two were splicing defects (IVS10+2T>G; IVS12+1G>C), one was a nonsense (c.384G>A=p.W128X) and one a missense mutation (c.848T>A=I283N). This is the first study of the molecular genetics of Variegate Porphyria in patients of Italian origin, and the finding of six novel mutations out of nine identified confirms the genetic heterogeneity observed for this disorder.

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Identification of the First Variegate Porphyria Mutation in an Indigenous Black South African and Further Evidence for Heterogeneity in Variegate Porphyria

Corrigall

Hift

Davids

et al. 2001

Molecular Genetics and Metabolism

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Three novel mutations in the protoporphyrinogen oxidase gene in Japanese patients with variegate porphyria

Cited by 6 publications

References 24 publications

Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria

Nine novel mutations in the protoporphyrinogen oxidase gene in Swedish families with variegate porphyria

Genetic analysis of Variegate Porphyria (VP) in Italy: Identification of six novel mutations in the protoporphyrinogen oxidase (PPOX) gene

Identification of the First Variegate Porphyria Mutation in an Indigenous Black South African and Further Evidence for Heterogeneity in Variegate Porphyria

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