Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants. (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants. (Articolo in rivista) (literal)

Anno

• 2008-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1016/j.bbadis.2008.01.012 (literal)

Alternative label

• Daniele, A;Cardillo, G;Pennino, C;Carbone, MT;Scognamiglio, D;Esposito, L;Correra, A;Castaldo, G;Zagari, A;Salvatore, F (2008)
  Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants.
  in Biochimica et biophysica acta. Molecular basis of disease
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Daniele, A;Cardillo, G;Pennino, C;Carbone, MT;Scognamiglio, D;Esposito, L;Correra, A;Castaldo, G;Zagari, A;Salvatore, F (literal)

Pagina inizio

• 378 (literal)

Pagina fine

• 384 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 1782 (literal)

Rivista

• Biochimica et biophysica acta. Molecular basis of disease (Rivista)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Univ Naples Federico 2, Dipartimento Biochim & Biotecnol Med, I-80131 Naples, Italy. CEINGE Biotecnol Avanzate Scari, I-80145 Naples, Italy. Univ Molise, Dipartimento Sci Salute, I-86100 Campobasso, Italy. Osped SS Annunziata, Ctr Screening Fenilchetonuria, I-80139 Naples, Italy. Naples Site CEINGE, European Sch Mol Med, SEMM, Naples, Italy. Univ Naples Federico 2, Dipartimento Sci Biol, I-80134 Naples, Italy. Univ Naples Federico 2, CNISM, I-80134 Naples, Italy. (literal)

Titolo

• Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants. (literal)

Abstract

• Hyperphenylalaninemia is a group of autosomal recessive disorders caused by a wide range of phenylalanine hydroxylase (PAH) gene variants. To study the effects of mutations on PAH activity, we have reproduced five mutations (p.N223Y, p.R297L, p.F382L, p.K398N and p.Q419R) that we recently identified in a population of Southern Italy. Transient expression of mutant full-length cDNAs in human HEK293 cells yielded PAH variants whose L-phenylalanine hydroxylase activity was between 40% and 70% that of the wild-type enzyme. Moreover, Western blot analysis revealed a 50-kD monomer in all mutants thereby indicating normal synthesis of the mutant proteins. Because of the clinical mild nature of the phenotypes we performed an in vivo BH4 loading test. This was positive in all tested patients, which indicates that they are likely to respond to the coenzyme in vivo. We also analysed the environment of each mutation site in the available crystal structures of PAH by using molecular graphics tools. The structural alteration produced by each mutation was elucidated and correlated to the mutated properties of the mutant enzymes. All the data obtained demonstrate the disease-causing nature of the five novel variants. (literal)

Prodotto di

• Institute of biostructure and bioimaging (IBB) (Istituto)

Autore CNR

• LUCIANA ESPOSITO (Unità di personale interno)
• ADRIANA ZAGARI (Unità di personale esterno)

Incoming links:

Autore CNR di

• LUCIANA ESPOSITO (Unità di personale interno)
• ADRIANA ZAGARI (Unità di personale esterno)

Prodotto

• Institute of biostructure and bioimaging (IBB) (Istituto)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Biochimica et biophysica acta. Molecular basis of disease (Rivista)