2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT.

We have examined the mutational basis of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency (MIM 102600) in a patient of Polish origin who has been passing 2,8-dihydroxyadenine (DHA) stones since birth, but has considerable residual enzyme activity in lymphocyte extracts. The five exons and flanking regions of APRT were amplified by PCR and then sequenced. A single T insertion was identified at the intron 4 splice donor site (TGgtaa to TGgttaa:IVS4+2insT) in one allele from the proband, his mother, and brother. A G-to-T transversion in exon 5 (GTC-to-TTC:c.448G>T, V150F) was identified in the other allele, and this mutation was also present in one allele from the father and the paternal grandmother. Tru91 and AvaII digestions of PCR products spanning exons 4 and 5, respectively, confirmed the mutations. The mother was heterozygous for an intragenic TaqI site, but all other family members were homozygous for the presence of this site. IVS4+2insT, located on the allele containing the TaqI site, has been identified previously in several families from Europe, suggesting a founder effect, but the substitution in exon 5 is a novel mutation. IVS4+2insT is known to result in complete loss of enzyme activity, and our results suggest that V150F produces an enzyme that is nonfunctional in vivo but has considerable residual activity in vitro.