Compound Heterozygous Hereditary Coproporphyria with Fluorescing Teeth

Groß, U.; Lamoril, J.; Kranl, Ch; Jacob, K.; Doss, M.; Silva, Y da; Freesemann, Anne G.; Deybach, Jean Charles; Sepp, Norbert; Nordmann, Y

doi:10.1177/000456329903600522

Cited by 12 publications

(7 citation statements)

References 10 publications

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“…Until now, a total of 34 different mutations had been identified in the CPO gene of patients suffering from HCP in heterozygous or homozygous form (Doss et al 1999;Lamoril et al 2001;Petersen et al 2000;Sassa et al 1997; Human Gene Mutation Database). In the present study, DGGE analysis and sequencing identified two novel and two previously reported mutations in five of nine investigated Swedish HCP families.…”

Section: Discussionmentioning

confidence: 99%

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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

2002

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Section: Discussionmentioning

confidence: 99%

“…Several HCP-coupled mutations have been identified in the CPO gene (Doss et al 1999;Lamoril et al 2001;Petersen et al 2000;Sassa et al 1997, and Human Gene Mutation Database). The mutations identified so far are, with a few exceptions, restricted to single families, making HCP a genetically heterogeneous disease.…”

Section: Introductionmentioning

confidence: 99%

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

2002

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“…Presentation with skin lesions alone is uncommon among patients with HCP; the few cases reported have usually been associated with hepatobiliary dysfunction (Brodie et al 1977;Hawk et al 1978;Martasek 1998). In contrast, the very rare homozygous form of HCP presents in childhood with skin lesions Martasek et al 1994b;Doss et al 1999). Harderoporphyria is characterized by neonatal hemolytic anemia, sometimes ac-companied by skin lesions and accumulation of harderoporphyrin in feces (Nordmann et al 1983;Lamoril et al 1995;Lamoril et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Mutations in the CPO Gene in British Patients Demonstrates Absence of Genotype-Phenotype Correlation and Identifies Relationship between Hereditary Coproporphyria and Harderoporphyria

Lamoril

Puy

Whatley

et al. 2001

The American Journal of Human Genetics

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Hereditary coproporphyria (HCP) is the least common of the autosomal dominant acute hepatic porphyrias. It results from mutations in the CPO gene that encodes the mitochondrial enzyme, coproporphyrinogen oxidase. A few patients have also been reported who are homoallellic or heteroallelic for CPO mutations and are clinically distinct from those with HCP. In such patients the presence of a specific mutation (K404E) on one or both alleles produces a neonatal hemolytic anemia that is known as "harderoporphyria"; mutations on both alleles elsewhere in the gene give rise to the "homozygous" variant of HCP. The molecular relationship between these disorders and HCP has not been defined. We describe the molecular investigation and clinical features of 17 unrelated British patients with HCP. Ten novel and four previously reported CPO mutations, together with three previously unrecognized single-nucleotide polymorphisms, were identified in 15 of the 17 patients. HCP is more heterogeneous than other acute porphyrias, with all but one mutation being restricted to a single family, with a predominance of missense mutations (10 missense, 2 nonsense, 1 frameshift, and 1 splice site). Of the four known mutations, one (R331W) has previously been reported to cause disease only in homozygotes. Heterologous expression of another mutation (R401W) demonstrated functional properties similar to those of the K404E harderoporphyria mutation. In all patients, clinical presentation was uniform, in spite of the wide range (1%-64%) of residual coproporphyrinogen oxidase activity, as determined by heterologous expression. Our findings add substantially to knowledge of the molecular epidemiology of HCP, show that single copies of CPO mutations that are known or predicted to cause "homozygous" HCP or harderoporphyria can produce typical HCP in adults, and demonstrate that the severity of the phenotype does not correlate with the degree of inactivation by mutation of coproporphyrinogen oxidase.

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“…CPOX gene mutation analysis revealed that our patient was homozygous for the previously described missense mutation c.980A>G (Doss et al 1999) which predicts the substitution of a highly conserved histidine (Figure 1) by an arginine at amino acid 327 (p.H327R) in the CPOX enzyme subunit. Our proband’s asymptomatic parents and four year old healthy sibling were heterozygous for the mutation, consistent with their having autosomal dominant HCP (typically non-penetrant).…”

Section: Discussionmentioning

confidence: 66%

“…Sequencing of the family’s CPOX gene identified homozygosity for the missense mutation, p.R231W (renumbered p.R331W by Delfau-Larue et al 1994), predicting an arginine to tryptophan substitution (Martasek et al 1994). Doss et al (1999) described a 10 year old girl who had homozygous HCP. She presented with skin fragility, erythema and scarring of hands and feet, and erythrodontia.…”

Section: Introductionmentioning

confidence: 99%

Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R

Hasanoğlu

Balwani

Kasapkara

et al. 2010

J of Inher Metab Disea

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Summary Hereditary coproporphyria (HCP) is an autosomal dominant acute hepatic porphyria due to the half-normal activity of the heme biosynthetic enzyme, coproporphyrinogen oxidase (CPOX). The enzyme catalyzes the step-wise oxidative decarboxylation of the heme precursor, coproporphyrinogen III to protoporphyrinogen IX via a tricarboxylic intermediate, harderoporphyrinogen. In autosomal dominant HCP, the deficient enzymatic activity results primarily in the accumulation of coproporphyrin III. To date, only a few homozygous HCP patients have been described, most having Harderoporphyria, a rare variant due to specific CPOX mutations that alter enzyme residues D400-K404, most patients described to date having at least one K404E allele. Here, we describe a Turkish male infant, the product of a consanguineous union, who presented with the Harderoporphyria phenotype including neonatal hyperbilirubinemia, hemolytic anemia, hepatosplenomegaly, and skin lesions when exposed to UV light. He was homoallelic for the CPOX missense mutation, c.980A>G (p.H327R), and had massively increased urinary uroporphyrins I and III (9250 and 2910 μM, respectively) and coproporphyrins I and III (895 and 19,400 μM, respectively). The patient expired at five months of age from an apparent acute neurologic porphyric attack. Structural studies predicted that p.H327R interacts with residue W399 in the CPOX active site, thereby accounting for the Harderoporphyria phenotype.

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Compound Heterozygous Hereditary Coproporphyria with Fluorescing Teeth

Cited by 12 publications

References 10 publications

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

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

Characterization of Mutations in the CPO Gene in British Patients Demonstrates Absence of Genotype-Phenotype Correlation and Identifies Relationship between Hereditary Coproporphyria and Harderoporphyria

Harderoporphyria due to homozygosity for coproporphyrinogen oxidase missense mutation H327R

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