A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects.
Adenine phosphoribosyltransferase (APRT) deficiency is a genetic disorder which causes 2,8-dihydroxy-adenine urolithiasis. The estimated incidence of heterozygosity in Caucasian and Japanese populations is 1%. Mutant alleles responsible for the disease have been classified as APRT*Q0 (type I) and APRT* (type II). In our previous study, we demonstrated in APRT*J a single common base change which accounts for 70% of the Japanese mutants. The present report describes the analysis of an APRT*Q0 mutation in Japanese subjects. Two nucleotide substitutions common to all seven affected alleles from four unrelated subjects (three homozygotes and a heterozygote) were identified: G----A at nucleotide position 1453 and C----T at 1456. The G----A altered the amino acid Trp98 to a stop codon. The C----T did not alter Ala99. These point mutations were demonstrated by sequence analysis of polymerase chain reaction (PCR)-amplified genomic DNA and cDNA. The G----A change at 1453 results in the elimination of a PflMI site in the APRT gene. PflMI digests, which were used to confirm the G----A transition, can be useful in screening for this specific mutation.
Mimori
A
A
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0358.
Hidaka
Y
Y
Wu
V C
VC
Tarlé
S A
SA
Kamatani
N
N
Kelley
W N
WN
Pallela
T D
TD
D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D015342:DNA Probes; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
D015342:DNA Probes; D000228:Adenine Phosphoribosyltransferase