title: Adenine phosphoribosyltransferase (APRT) deficiency: identification of a novel nonsense mutation.
abstract: BACKGROUND
  Adenine phosphoribosyltransferase deficiency (APRTD) is an under estimated genetic form of kidney stones and/or kidney failure, characterized by intratubular precipitation of 2,8-dihydroxyadenine crystals (2,8-DHA). Currently, five pathologic allelic variants have been identified as responsible of the complete inactivation of APRT protein.
  
  
  METHODS
  In this study, we report a novel nonsense mutation of the APRT gene from a 47- year old Italian patient. The mutation, localized in the exon 5, leads to the replacement of a cytosine with a thymine (g.2098C > T), introducing a stop codon at amino acid position 147 (p.Gln147X).This early termination was deleterious for the enzyme structural and functional integrity, as demonstrated by the structure analysis and the activity assay of the mutant APRT protein.
  
  
  CONCLUSIONS
  These data revealed that the p.Gln147X mutation in APRT gene might be a new cause of APRT disease.
authors.affiliation: Research Laboratories - Molecular Biology, IRCCS Policlinico San Donato, Piazza E, Malan 2, 20097, San Donato Milanese, Milan, Italy. rea.valaperta@grupposandonato.it.
authors.forename: Rea
authors.initials: R
authors.lastname: Valaperta
authors.forename: Vittoria
authors.initials: V
authors.lastname: Rizzo
authors.forename: Fortunata
authors.initials: F
authors.lastname: Lombardi
authors.forename: Chiara
authors.initials: C
authors.lastname: Verdelli
authors.forename: Marco
authors.initials: M
authors.lastname: Piccoli
authors.forename: Andrea
authors.initials: A
authors.lastname: Ghiroldi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Creo
authors.forename: Alessio
authors.initials: A
authors.lastname: Colombo
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Valisi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Margiotta
authors.forename: Rossella
authors.initials: R
authors.lastname: Panella
authors.forename: Elena
authors.initials: E
authors.lastname: Costa
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D017433:Protein Structure, Secondary; D052878:Urolithiasis / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D000228:Adenine Phosphoribosyltransferase