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

Corrigall, Anne V.; Hift, Richard; Davids, Lester M.; Hancock, Valerie; Meissner, D.; Kirsch, Ralph E.; Meissner, Peter N.

doi:10.1006/mgme.2001.3163

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…The new HEP patient came from an area of Africa from which no other cases of porphyria have been described to date. With the exception of South Africa 18,19 there are few reports of cutaneous porphyrias among indigenous Africans, the prevalence of these rare diseases and the role of precipitating factors such as malaria and viral infections being essentially unknown.…”

Section: Discussionmentioning

confidence: 99%

Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene

To‐Figueras¹,

Phillips²,

Gonzalez-López³

et al. 2011

British Journal of Dermatology

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Summary Background Hepatoerythropoietic porphyria (HEP) is a rare form of porphyria that results from a deficiency of uroporphyrinogen decarboxylase (UROD). The disease is caused by homoallelism or heteroallelism for mutations in the UROD gene. Objective To study a 19 year-old woman from Equatorial Guinea, one of the few cases of HEP of African descent and to characterize a new mutation causing HEP. Methods Excretion of porphyrins and residual UROD activity in erythrocytes were measured and compared to other HEP patients. UROD gene of the proband was sequenced and a new mutation identified. The recombinant UROD protein was purified and assayed for enzymatic activity. The aminoacid change mapped to the UROD protein and the functional consequences were predicted. Results The patient presented a novel G170D missense mutation in homozygosity. Porphyrin excretion showed an atypical pattern in stool with a high pentaporphyrin III to isocoproporphyrin ratio. Erythrocyte UROD activity was 42 % of normal and higher than the activity found in HEP patients with a G281E mutation. The recombinant UROD protein showed a relative activity of 17 % and 60 % of wild-type towards uroporphyrinogen I and III respectively. Molecular modelling showed that glycine 170 is located on the dimer interface of UROD, in a loop containing residues 167-172 that are critical for optimal enzymatic activity and that carboxyl side chain from aspartic acid is predicted to cause negative interactions between the protein and the substrate. Conclusions The results emphasize the complex relationship between the genetic defects and the biochemical phenotype in homozygous porphyria.

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Section: Discussionmentioning

confidence: 99%

Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene

To‐Figueras¹,

Phillips²,

Gonzalez-López³

et al. 2011

British Journal of Dermatology

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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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“…(8) Although only few genetic studies in patients with VP or AIP have been performed in South Africa, these have identified novel mutations amongst black individuals and provide evidence for heterogeneity of molecular abnormalities in different populations. (7,26) Robreau-Fraolini et al (2000) performed the first porphobilinogen deaminase gene study within a black population, demonstrating that the spectrum of mutations differ compared to those found in white counterparts. (27) They identified four novel mutations and further discovered that certain single nucleotide polymorphisms existed only in black individuals and not in whites.…”

Section: Discussionmentioning

confidence: 99%

Porphyric neuropathy in black South Africans: a case series

Koufos¹,

Modi²

2023

Wits Journal of Clinical Medicine

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Porphyria is a rare disorder that results from mutations in the genes important in haem biosynthesis. Several types are described. Acute attacks lead to central, autonomic and peripheral nervous system manifestations. These acute attacks typically occur in acute intermittent porphyria, and less so in variegate porphyria. The neuropathy in this condition can mimic Guillain-Barré syndrome (GBS), and is often misdiagnosed and incorrectly treated. It is rare in general, but considered to be extremely uncommon in the black African population. We describe five black South African patients, three of whom were diagnosed with variegate porphyria, with the presenting manifestation of a severe neuropathy. The neuropathy was atypical in nature and variable in presentation and highlight the importance of considering porphyria in such patients.

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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

Cited by 9 publications

References 20 publications

Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene

Hepatoerythropoietic porphyria due to a novel mutation in the uroporphyrinogen decarboxylase gene

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

Porphyric neuropathy in black South Africans: a case series

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