Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe an apparent hotspot for spontaneous deletions and base substitution mutations at a TTC trinucleotide direct repeat/MboII restriction site in exon 5 of the Chinese hamster APRT gene, in a region with the potential to form a relatively stable, quasipalindromic, stem-loop structure. The recurrent 3 bp TTC deletions observed at this site, which account for approx. 20% of the characterized spontaneous APRT deletions in hemizygous CHO cell lines, represent the only spontaneous deletion events that have been recovered more than once at this locus. A total of 11 independently derived, spontaneous CHO cell APRT mutants with identical 3 bp TTC deletions at this exon 5 MboII site, plus another five mutants that have single base substitutions at this site have been identified among spontaneous mutant collections in several different laboratories. Intriguingly, each of the frequently deleted or mutated bases at this exon 5 deletion hotspot site would correspond to one of the unpaired bases within a single-stranded 'loop' region of a stable, quasipalindromic, stem-loop structure that can be formed by intrastrand pairing of inverted repeats in this portion of the APRT gene sequence. An identical TTC trinucleotide direct repeat sequence at the same site in exon 5 of the human APRT gene also appears to be a hotspot for spontaneous deletion.
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PMID:Characterization of an apparent hotspot for spontaneous mutation in exon 5 of the Chinese hamster APRT gene. 867 21

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.
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PMID:2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT. 1124 33