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 analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency in Japanese patients. Among 141 defective APRT alleles from 72 different families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and duplication of a 4-bp sequence in exon 3, respectively. The disease-causing mutations of only four (3%) of all the alleles among Japanese remain to be elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient patients by identifying only three disease-causing mutations. All of the different alleles with the same mutation had the same haplotype, except for APRT*J alleles, thereby suggesting that alleles with the same mutation in different families were derived from the same ancestral gene. Evidence for a crossover or gene conversion event within the APRT gene was observed in an APRT*J mutant allele. Distribution of mutant alleles encoding APRT deficiency among the Japanese was similar to that seen in cystic fibrosis genes among Caucasians and Tay-Sachs genes among the Ashkenazi Jews.
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PMID:Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients. 135 80

About 79% of all the Japanese patients with adenine phosphoribosyltransferase (APRT) deficiency have been estimated to possess at least one APRT*J allele with a substitution of ACG for ATG at codon 136. We developed a non-radioactive method for diagnosing genotypes of this disease. Part of the genomic DNA including the mutation site of the APRT*J allele was amplified using polymerase chain reaction and the amplified product was dot-blotted onto nylon membranes and then hybridized with either APRT*J-specific or non-APRT*J-specific synthetic oligonucleotides labelled at the 5' termini with biotin in the presence of non-labelled competitive synthetic sequences. The temperature was gradually decreased during the hybridization. When competitive sequences were omitted, difference in the intensity of the hybridization between APRT*J-containing and non-containing samples was not sufficiently clear to differentiate the genotypes. When an excess amount of competitive sequences was added in addition to biotin-labelled oligonucleotides, this method effectively differentiated samples containing only APRT*J alleles from those containing only non-APRT*J alleles. The present method was also useful to differentiate samples with both APRT*J and non-APRT*J alleles from those having only either of the alleles. An equivalent procedure using competitive sequence for hybridization and gradually decreasing the temperature will be useful for detecting point mutations in other genes.
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PMID:Detection of the most common mutation of adenine phosphoribosyltransferase deficiency among Japanese by a non-radioactive method. 177 79

Homozygous deficiency of a purine salvage enzyme, adenine phosphoribosyltransferase (APRT), causes urolithiasis and renal failure. There are two known types of homozygous APRT deficiencies; type I patients completely lack APRT activity while type II patients only partially lack such activity. All type II patients possess at least one APRT*J allele with a substitution from ATG (Met) to ACG (Thr) at codon 136. Type I patients are considered to possess two alleles (APRT*Q0) both of which code for complete deficiencies. Thus, some patients with type II APRT deficiencies may have a genotype of APRT*J/APRT*Q0. As no individuals with such a genotype have previously been identified, we performed extensive analysis on four members of a family by (1) the T-cell method for the identification of a homozygote, (2) the B-cell method for the identification of heterozygotes, and (3) oligonucleotide hybridization after in vitro amplification of a part of genomic APRT sequence for the identification of APRT*J and non-APRT*J alleles. We report here the first evidence that 2,8-dihydroxyadenine urolithiasis developed in a boy aged 2 years with a genotype of APRT*J/APRT*Q0.
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PMID:Identification of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APART*Q0) leading to 2,8-dihydroxyadenine urolithiasis. 222 34

The incidence of adenine phosphoribosyltransferase (APRT) deficiency is higher among Japanese nationals than among other ethnic groups, and the most common mutation (APRT*J, ATG to ACG mutation at codon 136) accounts for 68% of the disease-causing genes among Japanese. To investigate the origin of these mutations, we studied the geographical distribution of the mutant genes in Japan. The APRT*J mutation is distributed nearly uniformly in the four main islands of Japan and Okinawa, suggesting a very early origin. The products of PCR amplification between positions 2344 and 2750 of the genomic APRT sequence were examined by SSCP analysis in random blood samples from Japanese, Korean, and Taiwanese nationals. Among 955 random Japanese blood samples, 7 (0.73%) were heterozygous for the APRT*J mutation, giving a calculated heterozygote frequency of 1.1% among Japanese for the entire APRT deficiency. None of 231 Taiwanese samples contained heterozygotes for the APRT*J mutation, while 2 (0.53%) of 356 Korean samples were heterozygous. In addition to the APRT*J sequence, a total of five variant sequences was found. Sequencing one variant revealed a base substitution in intron 4, suggesting therefore that they are harmless mutations. Since the APRT*J mutation is present in Koreans and Okinawans who share ancestors only before the Yayoi era (third century BC to third century AD), the origin of the APRT*J mutation predates 300 BC.
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PMID:The origin of the most common mutation of adenine phosphoribosyltransferase among Japanese goes back to a prehistoric era. 888 82