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Titolo:
Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects. Identification of five novel mutations, one of them causing instability of the protein
Autore:
Richard, E; Desviat, LR; Perez, B; Perez-Cerda, C; Ugarte, M;
Indirizzi:
Univ Autonoma Madrid, CSIC, Dept Biol Mol, E-28049 Madrid, Spain Univ Autonoma Madrid Madrid Spain E-28049 iol Mol, E-28049 Madrid, Spain UnivnAutonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spai Univ Autonoma Madrid Madrid Spain E-28049 ro Ochoa, E-28049 Madrid, Spai
Titolo Testata:
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
fascicolo: 3, volume: 1453, anno: 1999,
pagine: 351 - 358
SICI:
0925-4439(19990330)1453:3<351:GHIPAP>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
COA CARBOXYLASE; BETA-SUBUNIT; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; DEHYDROGENASE; EXON; COMPLEMENTATION; FIBROBLASTS; DELETION; ENZYME;
Keywords:
mutation; propionic acidemia; PCCA gene; mitochondrial import; mitochondrial stability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Ugarte, M Univ Autonoma Madrid, CSIC, Dept Biol Mol, E-28049 Madrid, SpainUniv Autonoma Madrid Madrid Spain E-28049 -28049 Madrid, Spain
Citazione:
E. Richard et al., "Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects. Identification of five novel mutations, one of them causing instability of the protein", BBA-MOL BAS, 1453(3), 1999, pp. 351-358

Abstract

The inherited metabolic disease propionic acidemia (PA) can result from mutations in either of the genes PCCA or PCCB, which encode the alpha and beta subunits, respectively, of the mitochondrial enzyme propionyl CoA-carboxylase. In this work we have analyzed the molecular basis of PCCA gene defects, studying mRNA levels and identifying putative disease causing mutations. A total of 10 different mutations, none predominant, are present in a sample of 24 mutant alleles studied. Five novel mutations are reported here forthe first time. A neutral polymorphism and a variant allele present in thegeneral population were also detected. To examine the effect of a point mutation (M348K) involving a highly conserved residue, we have carried out invitro expression of normal and mutant PCCA cDNA and analyzed the mitochondrial import and stability of the resulting proteins. Both wild-type and mutant proteins were imported into mitochondria and processed into the mature form with similar efficiency, but the mature mutant M348K protein decayed more rapidly than did the wild-type, indicating a reduced stability, which is probably the disease-causing mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.

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Documento generato il 04/04/20 alle ore 11:02:43