| http://purl.uniprot.org/citations/32333439 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32333439 | http://www.w3.org/2000/01/rdf-schema#comment | "Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298-2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation-specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation-specific treatments for PKU."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.24026"xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Castro M."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Martinez A."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Campistol J."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Artuch R."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Leal F."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Garcia I."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Navarrete R."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Perez B."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Ugarte M."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Gil D."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Desviat L.R."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Gamez A."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Morais A."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Cornejo V."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Belanger-Quintana A."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Gallego D."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Alcaide C."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Yahyaoui R."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Bueno-Delgado M."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Pedron-Giner C."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Sanchez-Lijarcio O."xsd:string |
| http://purl.uniprot.org/citations/32333439 | http://purl.uniprot.org/core/author | "Vitoria I."xsd:string |