Two novel mutations and coexistence of the 991C.T and the 1339C.T mutation on a single allele in the coproporphyrinogen oxidase gene in Swedish patients with hereditary coproporphyria

Wiman, Åsa; Flodérus, Ylva; Harper, Pauline

doi:10.1007/s100380200059

Cited by 9 publications

(8 citation statements)

References 19 publications

(22 reference statements)

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“…In Swedish carriers of the AIP mutation, W198X, the clinical penetrance among individuals >18 years of age was found to be as high as 44% (52). In a group of five HCP families in whom the underlying mutation was identified, a very high biochemical and/or clinical penetrance was observed (37). In the present study, only two adults were found to be silent carriers of the VP trait.…”

Section: Discussionsupporting

confidence: 38%

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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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Section: Discussionsupporting

confidence: 38%

“…For detection of identified sequence variations in additional family members and for haplotype analysis, restriction enzyme cleavage or denaturating-gradient gel electrophoresis (DGGE) was used. The DGGE technique was the same as previously described for detecting HCP mutations in the CPO gene (37).…”

Section: Dna Methodsmentioning

confidence: 99%

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

2003

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“…The prevalence of HCP in Sweden has been estimated to be 1:200,000 and four mutations (two novel) have been reported in Swedish families (9). Since this study, the gene defects in two more families have been identified with DNA sequencing and so far no case of a homozygous or compound heterozygous genotype has been identified.…”

mentioning

confidence: 89%

“…1). The biochemical investigations and the CPOX gene analysis used by our group have been previously described (9).…”

Section: Patientsmentioning

confidence: 99%

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Identification of an AluY‐mediated deletion of exon 5 in the CPOX gene by MLPA analysis in patients with hereditary coproporphyria

et al. 2011

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Hereditary coproporphyria (HCP) is an autosomal dominantly inherited hepatic porphyria, caused by a mutation in the coproporphyrinogen oxidase (CPOX) gene. The genetic defect leads to a partial defect of CPOX, the sixth enzyme involved in haem biosynthesis. Affected individuals can develop acute life-threatening attacks of neurovisceral symptoms and/or more rarely cutaneous symptoms such as skin fragility and blistering. The identification of the genetic defect in HCP families is of crucial importance to detect the carrier status which allows counselling to prevent possible triggering factors, e.g. certain drugs, alcohol, or fasting. In a total of nine Swedish HCP families, routine gene sequence analysis had identified a causative mutation in only five. In the present study, using an in-house developed synthetic probe set for multiplex ligation-dependent probe amplification (MLPA) analysis, we detected a deletion of the fifth exon in the CPOX gene in the remaining four families. The deletion is 3381 bp in size and has originated by an Alu-mediated mechanism. This finding emphasizes the usefulness of MLPA analysis as a complement to gene sequencing for comprehensive genetic diagnostics in HCP patients.

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Porphyrias

Mascaró¹,

Lim²

2011

Harper's Textbook of Pediatric Dermatology

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Two novel mutations and coexistence of the 991C.T and the 1339C.T mutation on a single allele in the coproporphyrinogen oxidase gene in Swedish patients with hereditary coproporphyria

Cited by 9 publications

References 19 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

Identification of an AluY‐mediated deletion of exon 5 in the CPOX gene by MLPA analysis in patients with hereditary coproporphyria

Porphyrias

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