Description:
ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY; APRTD
ADENINE PHOSPHORIBOSYLTRANSFERASE; APRT 2,8-@DIHYDROXYADENINE UROLITHIASIS, INCLUDED
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Nucleotide and Nucleic Acid Metabolism |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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Asian
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Ethnicity
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JAPANESE
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Relation to Proband
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proband
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Confirmation
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Biochemical characterization before cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| adenine phosphoribosyltransferase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 2.4.2.7; 25% activity. |
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| Gene |
APRT |
| Chromosomal Location |
16q24 |
| Allelic Variant 1 |
102600.0003; APRT DEFICIENCY, JAPANESE TYPE |
| Identified Mutation |
MET136THR; Hidaka et al. (1988) identified a T-to-C substitution in exon 5 at position 2069, giving rise to substitution of threonine for methionine at position 136 in the Japanese-type APRT deficiency. The enzyme showed abnormal kinetics and activity that was less than 10.3% of normal. Six other Japanese homozygotes carried the same mutation on at least 1 allele. In the Japanese type of APRT deficiency, Kamatani et al. (1989) took advantage of the fact that the only methionine residue in normal APRT (at position 136) has been changed to threonine. By means of specific cleavage of the peptide at the methionine residue with cyanogen bromide (BrCN), they could distinguish normal from mutant proteins. Kamatani et al. (1989) found that 79% of all Japanese patients with this disease and more than half of the world's patients have this particular mutation. Kamatani et al. (1990) found that 24 of 39 Japanese 2,8-dihydroxyadenine urolithiasis patients had only APRT*J alleles. They found that normal alleles occur in 4 major haplotypes, whereas all APRT*J alleles occurred in only 2. They interpreted this as meaning that all APRT*J alleles had a single origin and that this mutant sequence has been maintained for a long time, as reflected in the frequency of the recombinant alleles. Sahota et al. (1991) described DHA-lithiasis in a patient heterozygous for the Japanese mutation. Lithiasis had previously been observed only in homozygotes. The polyamine pathway is thought to be the major source of endogenous adenine in the human. Whether increased polyamine synthesis can lead to increased adenine production, enhancer to DHA-lithiasis in an APRT heterozygote, remains to be determined. Among 141 defective APRT alleles from 72 different Japanese families, Kamatani et al. (1992) found the met136-to-thr mutation in 96 (68%); 30 (21%) and 10 (7%) had the TGG-to-TGA nonsense mutation at codon 98 (102600.0005) and duplication of a 4-bp sequence in exon 3 (102600.0006), respectively.
Kamatani et al. (1996) noted that the APRT*J mutation is distributed nearly uniformly on the 4 main islands of Japan and Okinawa, suggesting a very early origin. Among 955 random Japanese blood samples, 7 (0.73%) were heterozygous for the APRT*J mutation. None of 231 Taiwanese samples contained heterozygotes for this mutation, whereas 2 (0.53%) of 356 Korean samples were heterozygous. Since the APRT*J mutation was found in Koreans and Okinawans who shared ancestors only before the Yayoi era (third century B.C. to third century A.D.), the origin of the APRT*J mutation predates 300 B.C.
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| Gene |
APRT |
| Chromosomal Location |
16q24 |
| Allelic Variant 2 |
102600.0003; APRT DEFICIENCY, JAPANESE TYPE |
| Identified Mutation |
MET136THR; Hidaka et al. (1988) identified a T-to-C substitution in exon 5 at position 2069, giving rise to substitution of threonine for methionine at position 136 in the Japanese-type APRT deficiency. The enzyme showed abnormal kinetics and activity that was less than 10.3% of normal. Six other Japanese homozygotes carried the same mutation on at least 1 allele. In the Japanese type of APRT deficiency, Kamatani et al. (1989) took advantage of the fact that the only methionine residue in normal APRT (at position 136) has been changed to threonine. By means of specific cleavage of the peptide at the methionine residue with cyanogen bromide (BrCN), they could distinguish normal from mutant proteins. Kamatani et al. (1989) found that 79% of all Japanese patients with this disease and more than half of the world's patients have this particular mutation. Kamatani et al. (1990) found that 24 of 39 Japanese 2,8-dihydroxyadenine urolithiasis patients had only APRT*J alleles. They found that normal alleles occur in 4 major haplotypes, whereas all APRT*J alleles occurred in only 2. They interpreted this as meaning that all APRT*J alleles had a single origin and that this mutant sequence has been maintained for a long time, as reflected in the frequency of the recombinant alleles. Sahota et al. (1991) described DHA-lithiasis in a patient heterozygous for the Japanese mutation. Lithiasis had previously been observed only in homozygotes. The polyamine pathway is thought to be the major source of endogenous adenine in the human. Whether increased polyamine synthesis can lead to increased adenine production, enhancer to DHA-lithiasis in an APRT heterozygote, remains to be determined. Among 141 defective APRT alleles from 72 different Japanese families, Kamatani et al. (1992) found the met136-to-thr mutation in 96 (68%); 30 (21%) and 10 (7%) had the TGG-to-TGA nonsense mutation at codon 98 (102600.0005) and duplication of a 4-bp sequence in exon 3 (102600.0006), respectively.
Kamatani et al. (1996) noted that the APRT*J mutation is distributed nearly uniformly on the 4 main islands of Japan and Okinawa, suggesting a very early origin. Among 955 random Japanese blood samples, 7 (0.73%) were heterozygous for the APRT*J mutation. None of 231 Taiwanese samples contained heterozygotes for this mutation, whereas 2 (0.53%) of 356 Korean samples were heterozygous. Since the APRT*J mutation was found in Koreans and Okinawans who shared ancestors only before the Yayoi era (third century B.C. to third century A.D.), the origin of the APRT*J mutation predates 300 B.C.
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| Remarks |
Japanese; type II APRT deficiency; 2,8dihydroxyadenine urolithiasis with homozygosity for a mutant form of APRT; approximately 25% of normal APRT activity in lymphoid culture |
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