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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-8-12
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pubmed:abstractText |
Mutations in the uroporphyrinogen III synthase (UROS) gene cause congenital erythropoietic porphyria (CEP), an autosomal-recessive inborn error of erythroid heme biosynthesis. Clinical features of CEP include dermatologic and hematologic abnormalities of variable severity. The discovery of a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be modulated by sequence variations in the ALAS2 gene. We genotyped ALAS2 in 4 unrelated CEP patients exhibiting the same C73R/P248Q UROS genotype. The most severe of the CEP patients, a young girl, proved to be heterozygous for a novel ALAS2 mutation: c.1757 A > T in exon 11. This mutation is predicted to affect the highly conserved and penultimate C-terminal amino acid of ALAS2 (Y586). The rate of 5-aminolevulinate release from Y586F was significantly increased over that of wild-type ALAS2. The contribution of the ALAS2 gain-of-function mutation to the CEP phenotype underscores the importance of modifier genes underlying CEP. We propose that ALAS2 gene mutations should be considered not only as causative of X-linked sideroblastic anemia (XLSA) and XLDPP but may also modulate gene function in other erythropoietic disorders.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:BadenasCeliaC,
pubmed-author:BeaumontCaroleC,
pubmed-author:ClaytonJeromeJ,
pubmed-author:DelabyConstanceC,
pubmed-author:DeybachJean-CharlesJC,
pubmed-author:DucampSarahS,
pubmed-author:FerreiraGloria CGC,
pubmed-author:GedCecileC,
pubmed-author:GouyaLaurentL,
pubmed-author:HerreroCarmenC,
pubmed-author:LyoumiSaidS,
pubmed-author:PuyHerveH,
pubmed-author:To-FiguerasJordiJ,
pubmed-author:de VerneuilHubertH
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1443-51
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pubmed:meshHeading |
pubmed-meshheading:21653323-5-Aminolevulinate Synthetase,
pubmed-meshheading:21653323-Amino Acid Sequence,
pubmed-meshheading:21653323-Anemia, Sideroblastic,
pubmed-meshheading:21653323-Base Sequence,
pubmed-meshheading:21653323-Child, Preschool,
pubmed-meshheading:21653323-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:21653323-Family Health,
pubmed-meshheading:21653323-Female,
pubmed-meshheading:21653323-Genetic Diseases, X-Linked,
pubmed-meshheading:21653323-Genotype,
pubmed-meshheading:21653323-Humans,
pubmed-meshheading:21653323-Infant,
pubmed-meshheading:21653323-Kinetics,
pubmed-meshheading:21653323-Male,
pubmed-meshheading:21653323-Molecular Sequence Data,
pubmed-meshheading:21653323-Mutation, Missense,
pubmed-meshheading:21653323-Pedigree,
pubmed-meshheading:21653323-Porphyria, Erythropoietic,
pubmed-meshheading:21653323-Protoporphyria, Erythropoietic,
pubmed-meshheading:21653323-Sequence Homology, Amino Acid,
pubmed-meshheading:21653323-Severity of Illness Index,
pubmed-meshheading:21653323-Spectrophotometry,
pubmed-meshheading:21653323-Uroporphyrinogen III Synthetase,
pubmed-meshheading:21653323-Uroporphyrinogens
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pubmed:year |
2011
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pubmed:articleTitle |
ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria.
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pubmed:affiliation |
Biochemistry and Molecular Genetics Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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