Adenine phosphoribosyltransferase (APRT) deficiency: identification of a novel nonsense mutation
- Equal contributors
1 Research Laboratories - Molecular Biology, IRCCS Policlinico San Donato, Piazza E. Malan 2, 20097, San Donato Milanese, Milan, Italy
2 Department Molecular Medicine, Clinical Biochemistry Unit, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
3 Laboratory of Stem Cells for Tissue Engineering, IRCCS Policlinico San Donato, Milan, Italy
4 Service Lab, Fleming Research, Milan, Italy
5 Department of Nephrology, IRCCS Policlinico San Matteo, Pavia, Italy
6 Service of Laboratory Medicine, IRCCS Policlinico San Donato, Milan, Italy
BMC Nephrology 2014, 15:102 doi:10.1186/1471-2369-15-102Published: 1 July 2014
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.
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.
These data revealed that the p.Gln147X mutation in APRT gene might be a new cause of APRT disease.