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+102600 ICD+
  • SNOMEDCT: 124274002
 SNOMEDCT: 124274002
ADENINE PHOSPHORIBOSYLTRANSFERASE; APRT

Other entities represented in this entry:
UROLITHIASIS, 2,8-DIHYDROXYADENINE, INCLUDED
UROLITHIASIS, DHA, INCLUDED
NEPHROLITHIASIS, DHA, INCLUDED
APRT DEFICIENCY, INCLUDED; APRTD, INCLUDED

HGNC Approved Gene Symbol: APRT

Cytogenetic location: 16q24.3     Genomic coordinates (GRCh37): 16:88,875,876 - 88,878,341 (from NCBI)

Gene Phenotype Relationships
Location Phenotype Phenotype
MIM number
16q24.3 Urolithiasis, 2,8-dihydroxyadenine  

Clinical Synopsis

TEXT
Description
Adenine phosphoribosyltransferase (APRT; EC 2.4.2.7) catalyzes the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme for recycling of adenine into nucleic acids. Complete or partial deficiency of APRT can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA).

Clinical Features
Mutant forms of adenine phosphoribosyltransferase have been described by Kelley et al. (1968) and by Henderson et al. (1969) who found the inheritance to be autosomal. The heat-stable enzyme allele has a frequency of about 15% and the heat-labile enzyme allele a frequency of about 85%. Kelley et al. (1968) found apparent heterozygosity in 4 persons in 3 generations of a family. The level of enzyme activity ranged from 21 to 37%, requiring some special explanation. That the enzyme is a dimer is one possibility.

Fox et al. (1973) described a second family with partial deficiency of red cell APRT.

Delbarre et al. (1974) found deficiency of APRT in persons with gout but recognized that purine overproduction was not necessarily caused by the APRT deficiency.

Emmerson et al. (1975) described a family with autosomal inheritance of APRT deficiency. The proband was a 24-year-old woman who had suffered from recurrent gouty arthritis since the age of 11 years. She also demonstrated considerable, although asymptomatic, renal impairment with a creatinine clearance of one-third normal. Eleven other asymptomatic members of the family also demonstrated a similar reduction in APRT activity in erythrocyte lysates. The partially purified APRT enzyme in the proband showed no difference in Michaelis constants, heat stability, or electrophoresis.

Debray et al. (1976) observed a child with urolithiasis and complete deficiency of APRT. Both parents had partial deficiency.

Van Acker et al. (1977) described brothers with complete deficiency of APRT. They were detected because one of them had from birth excreted gravel consisting of stones of 2,8-dihydroxyadenine in urine. Neither showed hyperuricemia or gout. Treatment with allopurinol and a low purine diet stopped stone formation. Homozygotes can be detected by raised urinary adenine levels and absence of detectable red cell APRT.

Rappaport and DeMars (1973) identified clones of cells resistant to 2,6-diaminopurine (DAP) in skin fibroblast cultures derived from 13 of 21 normal humans. In some of the mutant cultures adenine phosphoribosyltransferase was normal. Two mutants from unrelated boys had little or no detectable APRT activity. Resistance resulted from reduced ability to convert DAP to its toxic ribonucleotide. The authors reasoned that mutant-yielding cultures were heterozygous to begin with. If so, DAP resistance has a heterozygote frequency as high as 0.2. This contrasts with the very low frequency of electrophoretic variants of APRT. There may be other mechanisms (mutation at other loci) for DAP-resistance. Azaguanine resistance is determined by mutation at the X-linked HPRT locus.

Barratt et al. (1979) reported a child of consanguineous Arab parents, the third case in which 2,8-dihydroxyadenine stones have been identified as the result of complete lack of APRT.

Kishi et al. (1984) found only 10 reported cases of complete deficiency of APRT, beginning with the case of Cartier et al. (1974). Kishi et al. (1984) reported 3 cases in 2 families. Although APRT deficiency occurred in mononuclear cells and polymorphonuclear leukocytes as well as in red cells, no abnormality of immunologic or phagocytic function was detected. The sole clinical manifestation was urinary calculi composed of 2,8-DHA.

In Japanese, partial deficiency of APRT leads to 2,8-dihydroxyadenine urolithiasis, whereas all Caucasian patients with 2,8-DHA urolithiasis have been completely deficient. Fujimori et al. (1985) found that partially purified enzyme from Japanese families has a reduced affinity for phosphoribosylpyrophosphate (PRPP), as well as increased resistance to heat and reduced sensitivity to the stabilizing effect of PRPP. They referred to this common Japanese mutant allele as APRT*J.

Kamatani et al. (1987) examined samples from 19 Japanese families with DHA-urolithiasis. In 15 of the 19 families, the patients had only partial APRT deficiency. All patients with DHA-urolithiasis were homozygotes regardless of whether the deficiency was complete or partial. They estimated that about 1% of the Japanese population are carriers. Kamatani et al. (1987) described a method for identifying heterozygotes for the Japanese allele of APRT.

Manyak et al. (1987) found DHA-urolithiasis in a 50-year-old white woman. The patient was homozygous for APRT deficiency.

Glicklich et al. (1988) reported the second case of homozygous APRT deficiency from the United States. The disorder was recognized 23 years after the patient, a black woman from Bermuda, had her initial episode of renal colic, and after 2,8-dihydroxyadenine stones had recurred after renal transplant.

Ishidate et al. (1991) reported father and daughter with DHA-urolithiasis. The father and his wife were first cousins; thus, this was an example of pseudodominance.

Gault et al. (1981) described 2,8-dihydroxyadenine urolithiasis in a white woman who lived in Newfoundland and first developed symptoms of urolithiasis at the age of 42. The use of infrared or x-ray diffraction analysis of calculi that are positive for uric acid with standard wet chemical tests can make the diagnosis. Adults may first present with renal failure. Renal biopsy shows changes like those of uric acid nephropathy.

Diagnosis
Maddocks and Al-Safi (1988) used identification of adenine in the urine by thin-layer chromatography to diagnose APRT deficiency.

Simmonds et al. (1992) pointed out that patients who are mistakenly diagnosed as having uric acid lithiasis will be treated successfully with allopurinol despite the incorrect diagnosis. This may be responsible for underdiagnosis of the disorder. Families carrying the mutant APRT gene need to be aware of it since acute renal failure may be the presenting symptom and this may be reversible, though some patients progress to chronic renal failure requiring dialysis and transplantation. Maddocks (1992) described a simple test for distinguishing uric acid calculi from 2,8-DHA calculi. Ward and Addison (1992) indicated that even visual examination can distinguish the two: 2,8-DHA stones are reddish-brown when wet and grayish when dry; they are also very soft and friable. Stones composed mainly of uric acid are very rare in children.

Laxdal and Jonasson (1988) found 2 children and 2 adults in 4 unrelated families with 2,8-dihydroxyadenine crystalluria. They suggested that the presence of round, brownish urine crystals, even without radiolucent kidney stones, should alert the physician to the diagnosis. Thirteen heterozygotes were identified by study of the families.

Laxdal (1992) pointed out that Iceland contributed 8 of the 62 APRT-deficient type I homozygotes. The 8 cases were from 8 different families. Although remote ancestral connections were identified, all 8 cases were detected by the finding of typical round reddish-brown crystals in the urine on light microscopy. The importance of alert laboratory technicians in making the diagnosis was emphasized.

Terai et al. (1995) detected homozygous APRT deficiency by the finding of 2,8-dihydroxyadenine-like spherical crystals in the urinary sediment. The molecular diagnosis was established using PCR-SSCP with the demonstration of the APRT*J allele (102600.0003).

Mapping
By cell hybridization studies, Tischfield and Ruddle (1974) concluded that the APRT locus is on chromosome 16. Marimo and Giannelli (1975) confirmed this assignment by demonstrating a 1.69-fold increase in enzyme level in trisomy 16 cells. The same cells showed no difference in the levels of HGPRT, G6PD (305900) or adenosine kinase (102750) from controls.

Barg et al. (1982) assigned APRT to 16pter-q12. Lavinha et al. (1984) assigned APRT and DIA4 (125860) to 16q12-q22 by study of rearranged chromosomes 16 in somatic cell hybrids. For APRT, Ferguson-Smith and Cox (1984) found a smallest region of overlap (SRO) of 16q22.2-q22.3.

Fratini et al. (1986) mapped the APRT locus with respect to the HP (140100) locus and the fragile site at 16q23.2 (FRA16D). A subclone of the APRT gene and a cDNA clone of HP were used for molecular hybridization to DNA from mouse-human hybrid cell lines containing specific chromosome 16 translocations. The APRT subclone was used for in situ hybridization to chromosomes expressing FRA16D. APRT was found to be distal to HP and FRA16D and was localized at 16q24, making the gene order cen--FRA16B--HP--FRA16D--APRT--qter.

Gene Structure
Broderick et al. (1987) found that in species as widely separated in evolution as man, mouse, hamster, and E. coli, CpG dinucleotides are conserved at a frequency higher than expected on the basis of randomness considering the G+C content of the gene. This suggested some importance of this sequence to the function of the gene. Although the intron I sequences of mouse and man had no apparent homology, both had retained a very high CpG content. The APRT gene is about 2.6 kb long and contains 5 exons. The promoter region of the human APRT gene, like that of several other 'housekeeping' genes, lacks the 'TATA' and 'CCAAT' boxes but contains 5 GC boxes that are potential binding sites for the Sp1 transcription factor.

Hidaka et al. (1987) also prepared a complete sequence of the APRT gene and found a number of discrepancies from the sequence reported by Broderick et al. (1987), all occurring within noncoding regions.

Population Genetics
Kamatani et al. (1992) stated that about 70 Japanese families with homozygous APRT deficiency have been reported, whereas the number of reported non-Japanese families is about 36. The estimated gene frequency among Japanese is about 1.2%.

Molecular Genetics
According to the numbering used by Hidaka et al. (1988), the adenine in the initiation codon ATG is counted as nucleotide number 1 and the initiator methionine is counted as amino acid number 1.

Hakoda et al. (1990) made the interesting observation that 2-step mutations leading to homozygous deficiencies at the somatic cell level, as proposed by the Knudson hypothesis of carcinogenesis in retinoblastoma (180200) and some other human tumors, occur at other autosomal loci. They cloned and enumerated somatic T cells with mutations at the APRT locus by taking advantage of the presence of heterozygous APRT deficiency and an effective selection procedure for homozygosity. They cultured peripheral blood mononuclear cells with 2,6-diaminopurine, an APRT-dependent cytotoxin, to search for in vivo mutational cells. In all 4 heterozygotes studied, homozygously deficient T cells were found, at an average frequency of 1.3 x 10(-4). Among 310 normal persons, Hakoda et al. (1990) identified only 1 homozygous APRT-deficient clone, with a calculated frequency of 5.0 x 10(-9). Homozygous cells were found at rather high frequencies in 15 putative heterozygotes, as reported by Hakoda et al. (1991). Analysis of genomic DNA in 82 resistant clones from 2 of the heterozygotes showed that 64 (78%) had lost the germinally intact alleles. This approach may prove useful for identifying heterozygotes for other enzyme deficiencies.

APRT Deficiency and Morquio Syndrome

Wang et al. (1999) described a Czech patient with Morquio syndrome (253000) who also had deficiency of APRT leading to 2,8-dihydroxyadenine urolithiasis. They pointed out that both GALNS (612222) and APRT are located on 16q24.3, suggesting that the patient had a deletion involving both genes. PCR amplification of genomic DNA indicated that a novel junction was created by the fusion of sequences distal to GALNS exon 2 and proximal to APRT exon 3, and that the size of the deleted region was approximately 100 kb. The deletion breakpoints were localized within GALNS intron 2 and APRT intron 2. Several other genes, including CYBA (608508), which is deleted or mutated in an autosomal form of chronic granulomatous disease (233690), are located in the 16q24.3 region. However, PCR amplification showed that the CYBA gene was present in the proband. Fukuda et al. (1996) described a Japanese patient with a submicroscopic deletion involving GALNS and APRT in one chromosome and a point mutation (R386C; 253000.0003) in the other GALNS allele. Wang et al. (1999) concluded that these findings indicated that APRT is located telomeric to GALNS, that GALNS and APRT are transcribed in the same orientation (centromeric to telomeric), and that combined APRT/GALNS deficiency may be more common than hitherto realized.

Animal Model
Engle et al. (1996) used targeted homologous recombination in embryonic stem cells to produce mice that lack APRT. Mice homozygous for a null Aprt allele excreted adenine and DHA crystals in their urine. Renal histopathology showed extensive tubular dilation, inflammation, necrosis, and fibrosis that varied in severity between different mouse backgrounds.

ALLELIC VARIANTS (Selected Examples):
Table View

.0001 APRT DEFICIENCY
APRT, PHE173DEL

In cell line '904,' a lymphoblastoid cell line from a Caucasian patient in Belgium, Hidaka et al. (1987) studied the molecular basis of APRT deficiency by sequencing both alleles of a patient with complete deficiency. In 1 allele, a trinucleotide deletion, TTC at positions 2179 to 2181 in exon 4, which corresponded to phenylalanine-173 in the deduced amino acid sequence, was demonstrated. In the other allele, a single nucleotide insertion, a T, was found immediately adjacent to the splice site at the 5-prime end of intron 4. This insertion led to aberrant splicing, as was demonstrated by the absence of exon 4 in the cDNA and by altered RNase mapping analysis of the abnormal mRNA. Frameshift led to premature termination at amino acid 110. The enzyme activity was less than 1% of normal and the enzyme protein was immunologically undetectable.

.0002 APRT DEFICIENCY
APRT, 1-BP INS, 1834T

In the second allele of cell line '904,' Hidaka et al. (1987) found insertion of a thymine at the 5-prime end of intron 4 between nucleotides 1834 and 1835 resulting in deletion of exon 4 and frameshift with premature termination at amino acid 110. The insertion changed the IVS4 splice donor site from gtaa to gttaa. In identical twin brothers born to nonconsanguineous German parents, Gathof et al. (1991) demonstrated that the cause of APRT deficiency was a single base insertion, a T, between bases 1831 and 1832 or 1832 and 1833. (In the numbering system they used, nucleotide 1831 is the first in intron 4. The insertion changed the donor site from gtaa to gttaa.) The insertion altered the consensus sequence at the splice donor site between exon 4 and intron 4, leading to aberrant splicing. They quoted finding of the same mutation in 2 other Caucasian patients living in the U.S. and as one of 2 alleles in a Belgian patient with compound heterozygosity. This is the same mutation as that found by Hidaka et al. (1987).

Menardi et al. (1997) demonstrated homozygosity for this common T insertion at the exon 4/intron 4 junction, resulting in the lack of exon 4 in the APRT mRNA. This common splice site mutation had always been found in association with a TaqI RFLP, leading to the proposal that this splice site mutation originated from a single event (Chen et al., 1993). However, Menardi et al. (1997) found a patient with this mutation who was negative for the TaqI RFLP. This faded the possibility of independent origins for this common type of mutation in Caucasians. They commented that the fact that the TaqI marker is only 840 bp from the mutation makes loss of the polymorphism through crossing over unlikely. Additionally, studies on somatic mutations at the APRT locus revealed the position of this T insertion to be a hotspot for mutational events (Chen et al., 1993).

.0003 APRT DEFICIENCY, JAPANESE TYPE
APRT, MET136THR [dbSNP:rs28999113]

This mutation had been designated APRT*J.

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 (3rd century B.C. to 3rd century A.D.), the origin of the APRT*J mutation predates 300 B.C.

.0004 APRT DEFICIENCY, COMPLETE, ICELANDIC TYPE
APRT, ASP65VAL [dbSNP:rs104894506]

Chen et al. (1990) analyzed the molecular nature of the mutation in all 5 patients with complete APRT deficiency reported from Iceland. The same mutation, an A-to-T transversion at position 1350, was identified in all of the patients (the A of the ATG start codon was designated number 1). The substitution led to the replacement of aspartic acid (GAC) by valine (GTC) at amino acid 65 in exon 3. In all 5 patients the mutation was homozygous. Common ancestors could be identified for only 2 of the cases.

.0005 APRT DEFICIENCY DUE TO TYPE I ALLELE
APRT, TRP98TER [dbSNP:rs104894507]

Mimori et al. (1991) analyzed 7 APRT*Q0 (null) alleles from 4 unrelated Japanese subjects (3 homozygotes and a heterozygote). In all 7, they found a G-to-A transition at nucleotide position 1453, which changed tryptophan-98 to a stop codon. There was also a C-to-T transition at 1456, which did not alter alanine-99. The G-to-A change at 1453 resulted in the elimination of a PflMI site in the APRT gene.

.0006 APRT DEFICIENCY
APRT, 4-BP DUP, EX3

Among 141 defective APRT alleles from 72 different Japanese families, Kamatani et al. (1992) found that 10 (7%) had duplication of a CCGA sequence in exon 3. Duplication resulted in an APRT*Q0 (null) allele. Two other alleles, APRT*J (102600.0003) and trp98-to-ter (102600.0005), accounted for 68% and 21%, respectively. The different alleles with the same mutation had the same haplotype, except for APRT*J. Evidence for a crossover or a gene conversion event within the APRT gene was observed in an APRT*J mutant allele.

.0007 APRT DEFICIENCY
APRT, LEU110PRO [dbSNP:rs104894508]

Sahota et al. (1994) described 2 sisters from Newfoundland who carried a leucine-to-proline missense transition at codon position 110 (nucleotide position 1759). One of the sisters exhibited 2,8-dihydroxyadenine urolithiasis, whereas the other was disease-free. Restriction mapping and DNA sequence data were compatible with both sisters being homozygous for the mutation, although hemizygosity could not be ruled out.

.0008 APRT DEFICIENCY
APRT, 254-BP DEL AND 8-BP INS

In a Caucasian patient with complete APRT deficiency, Menardi et al. (1997) found compound heterozygosity for the common T insertion at the IVS4 splice donor site (102600.0002) and a novel complex mutation involving simultaneous deletion/insertion and repair events. The mutation involved a deletion of 254 bp and an insertion of 8 bp exactly at the site of the deletion. Downstream of the mutations, Menardi et al. (1997) found a 14-bp sequence of inverse complementary to this insertion and 6 flanking nucleotides. A more detailed analysis of the region where the deletion had occurred revealed several informative sequence features suitable to explain how the mutation took place.

.0009 APRT DEFICIENCY
APRT, TER-SER

In a patient with APRT deficiency, Taniguchi et al. (1998) found that the physiologic stop codon of the gene, TGA, was replaced by TCA. This base substitution generated a new HinfI restriction site, and, using PCR and subsequent digestion by this enzyme, they could confirm that the patient was homozygous for the base substitution. The amount of mRNA in transformed B cells was approximately one-quarter of that in control subjects, and no APRT proteins were detected. In eukaryotes, unlike prokaryotes, no rescue systems for defective polypeptide termination caused by a missing stop codon have been found. Therefore, the outcome of the defect in this patient was unclear from present knowledge about termination of polypeptide synthesis. The stop codon was changed to a serine codon and the reading frame was extended to the poly(A) addition site. The poly(A) signal AGTAAA is located 213 nucleotides downstream of the physiologic stop codon, but there are no stop codons between them (Broderick et al., 1987).

See Also:
Doppler et al. (1981); Fox et al. (1977); Hidaka et al. (1987); Hirsch-Kauffmann and Doppler (1981); Johnson et al. (1977); Kamatani et al. (1990); Kamatani et al. (1987); Lester et al. (1980); Nesterova et al. (1987); Simmonds (1979); Simon and Taylor (1983); Takeuchi et al. (1985); Wilson et al. (1986)

REFERENCES
1. Barg, R., Barton, P., Caine, A., Clements, R. L., Ferguson-Smith, M. A., Malcolm, S., Morrison, N., Murphy, C. S. Regional localization of the human alpha-globin gene to the short arm of chromosome 16 (16p12-pter) using both somatic cell hybrids and in situ hybridization. Cytogenet. Cell Genet. 32: 252-253, 1982.

2. Barratt, T. M., Simmonds, H. A., Cameron, J. S., Potter, C. F., Rose, G. A., Arkell, D. G., Williams, D. I. Complete deficiency of adenine phosphoribosyltransferase: a third case presenting as renal stones in a young child. Arch. Dis. Child. 54: 25-31, 1979. [PubMed: 420519, related citations] [Full Text: Pubget]

3. Broderick, T. P., Schaff, D. A., Bertino, A. M., Dush, M. K., Tischfield, J. A., Stambrook, P. J. Comparative anatomy of the human APRT gene and enzyme: nucleotide sequence divergence and conservation of a nonrandom CpG dinucleotide arrangement. Proc. Nat. Acad. Sci. 84: 3349-3353, 1987. [PubMed: 3554238, related citations] [Full Text: HighWire Press, Pubget]

4. Cartier, P., Hamet, M., Hamburger, J. Une nouvelle maladie metabolique: le deficit complet en adenine phosphoribosyltransferase avec lithiase de 2,8-dihydroxyadenine. C. R. Seances Acad. Sci. 279: 883-886, 1974.

5. Chen, J., Sahota, A., Laxdal, T., Stambrook, P. J., Tischfield, J. A. Demonstration of a common mutation at the adenine phosphoribosyltransferase (APRT) locus in the Icelandic population. (Abstract) Am. J. Hum. Genet. 47 (suppl.): A152 only, 1990.

6. Chen, J., Sahota, A., Martin, G. F., Hakoda, M., Kamatani, N., Stambrook, P. J., Tischfield, J. A. Analysis of germline and in vivo somatic mutations in the human adenine phosphoribosyltransferase gene: mutational hot spots at the intron 4 splice donor site and at codon 87. Mutat. Res. 287: 217-225, 1993. [PubMed: 7685481, related citations] [Full Text: Elsevier Science, Pubget]

7. Debray, H., Cartier, P., Temstet, A., Cendron, J. Child's urinary lithiasis revealing a complete deficit in adenine phosphoribosyl transferase. Pediat. Res. 10: 762-766, 1976. [PubMed: 7766, related citations] [Full Text: Pubget]

8. Delbarre, F., Aucher, C., Amor, B., de Gery, A., Cartier, P., Hamet, M. Gout with adenine phosphoribosyltransferase deficiency. Biomedicine 21: 82-85, 1974. [PubMed: 4852180, related citations] [Full Text: Pubget]

9. Doppler, W., Hirsch-Kauffmann, M., Schabel, F., Schweiger, M. Characterization of the biochemical basis of a complete deficiency of the adenine phosphoribosyl transferase (APRT). Hum. Genet. 57: 404-410, 1981. [PubMed: 7286981, related citations] [Full Text: Pubget]

10. Emmerson, B. T., Gordon, R. B., Thompson, L. Adenine phosphoribosyltransferase deficiency: its inheritance and occurrence in a female with gout and renal disease. Aust. New Zeal. J. Med. 5: 440-446, 1975. [PubMed: 1061547, related citations] [Full Text: Pubget]

11. Engle, S. J., Stockelman, M. G., Chen, J., Boivin, G., Yum, M.-N., Davies, P. M., Ying, M. Y., Sahota, A., Simmonds, H. A., Stambrook, P. J., Tischfield, J. A. Adenine phosphoribosyltransferase-deficient mice develop 2,8-dihydroxyadenine nephrolithiasis. Proc. Nat. Acad. Sci. 93: 5307-5312, 1996. [PubMed: 8643571, related citations] [Full Text: HighWire Press, Pubget]

12. Ferguson-Smith, M. A., Cox, D. R. Report of the committee on the genetic constitution of chromosomes 13, 14, 15, 16 and 17. Cytogenet. Cell Genet. 37: 127-154, 1984. [PubMed: 6360556, related citations] [Full Text: Pubget]

13. Fox, I. H., Lacroix, S., Planet, G., Moore, M. Partial deficiency of adenine phosphoribosyltransferase in man. Medicine 56: 515-526, 1977. [PubMed: 335189, related citations] [Full Text: Pubget]

14. Fox, I. H., Meade, J. C., Kelley, W. N. Adenine phosphoribosyltransferase deficiency in man: report of a second family. Am. J. Med. 55: 614-619, 1973. [PubMed: 4749203, related citations] [Full Text: Elsevier Science, Pubget]

15. Fratini, A., Simmers, R. N., Callen, D. F., Hyland, V. J., Tischfield, J. A., Stambrook, P. J., Sutherland, G. R. A new location for the human adenine phosphoribosyltransferase gene (APRT) distal to the haptoglobin (HP) and fra(16)(q23) (FRA16D) loci. Cytogenet. Cell Genet. 43: 10-13, 1986. [PubMed: 3780312, related citations] [Full Text: Pubget]

16. Fujimori, S., Akaoka, I., Sakamoto, K., Yamanaka, H., Nishioka, K., Kamatani, N. Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies. Hum. Genet. 71: 171-176, 1985. [PubMed: 3876264, related citations] [Full Text: Pubget]

17. Fukuda, S., Tomatsu, S., Masuno, M., Ogawa, T., Yamagishi, A., Rezvi, G. M. M., Sukegawa, K., Shimozawa, N., Suzuki, Y., Kondo, N., Imaizumi, K., Kuroki, Y., Okabe, T., Orii, T. Mucopolysaccharidosis IVA: submicroscopic deletion of 16q24.3 and a novel R386C mutation of N-acetylgalactosamine-6-sulfate sulfatase gene in a classical Morquio disease. Hum. Mutat. 7: 123-134, 1996. [PubMed: 8829629, related citations] [Full Text: John Wiley & Sons, Inc., Pubget]

18. Gathof, B. S., Sahota, A., Gresser, U., Chen, J., Stambrook, P. J., Tischfield, J. A., Zollner, N. Identification of a splice mutation at the adenine phosphoribosyltransferase locus in a German family. Klin. Wschr. 69: 1152-1155, 1991.

19. Gault, M. H., Simmonds, H. A., Snedden, W., Dow, D., Churchill, D. N., Penney, H. Urolithiasis due to 2,8-dihydroxyadenine in an adult. New Eng. J. Med. 305: 1570-1572, 1981. [PubMed: 7311997, related citations] [Full Text: Atypon, Pubget]

20. Glicklich, D., Gruber, H. E., Matas, A. J., Tellis, V. A., Karwa, G., Finley, K., Salem, C., Soberman, R., Seegmiller, J. E. 2,8-Dihydroxyadenine urolithiasis: report of a case first diagnosed after renal transplant. Quart. J. Med. (N.S.) 69: 785-793, 1988.

21. Hakoda, M., Nishioka, K., Kamatani, N. Homozygous deficiency at autosomal locus APRT in human somatic cells in vivo induced by two different mechanisms. Cancer Res. 50: 1738-1741, 1990. [PubMed: 2306728, related citations] [Full Text: HighWire Press, Pubget]

22. Hakoda, M., Yamanaka, H., Kamatani, N., Kamatani, N. Diagnosis of heterozygous states for adenine phosphoribosyltransferase deficiency based on detection of in vivo somatic mutants in blood T cells: application to screening of heterozygotes. Am. J. Hum. Genet. 48: 552-562, 1991. [PubMed: 1998341, related citations] [Full Text: Pubget]

23. Henderson, J. F., Kelley, W. N., Rosenbloom, F. M., Seegmiller, J. E. Inheritance of purine phosphoribosyltransferases in man. Am. J. Hum. Genet. 21: 61-70, 1969. [PubMed: 5763607, related citations] [Full Text: Pubget]

24. Hidaka, Y., Palella, T. D., O'Toole, T. E., Tarle, S. A., Kelley, W. N. Human adenine phosphoribosyltransferase: identification of allelic mutations at the nucleotide level as a cause of complete deficiency of the enzyme. J. Clin. Invest. 80: 1409-1415, 1987. [PubMed: 3680503, related citations] [Full Text: Journal of Clinical Investigation, Pubget]

25. Hidaka, Y., Tarle, S. A., Fujimori, S., Kamatani, N., Kelley, W. N., Palella, T. D. Human adenine phosphoribosyltransferase deficiency: demonstration of a single mutant allele common to the Japanese. J. Clin. Invest. 81: 945-950, 1988. [PubMed: 3343350, related citations] [Full Text: Journal of Clinical Investigation, Pubget]

26. Hidaka, Y., Tarle, S. A., O'Toole, T. E., Kelley, W. N., Palella, T. D. Nucleotide sequence of the human APRT gene. Nucleic Acids Res. 15: 9086, 1987. [PubMed: 3684585, related citations] [Full Text: HighWire Press, Pubget]

27. Hirsch-Kauffmann, M., Doppler, W. Biochemical studies on a patient with complete APRT-deficiency. (Abstract) Sixth Int. Cong. Hum. Genet., Jerusalem 96 only, 1981.

28. Ishidate, T., Igarashi, S., Kamatani, N. Pseudodominant transmission of an autosomal recessive disease, adenine phosphoribosyltransferase deficiency. J. Pediat. 118: 90-91, 1991. [PubMed: 1986109, related citations] [Full Text: Pubget]

29. Johnson, L. A., Gordon, R. B., Emmerson, B. T. Adenine phosphoribosyltransferase: a simple spectrophotometric assay and the incidence of mutation in the normal population. Biochem. Genet. 15: 265-272, 1977. [PubMed: 869896, related citations] [Full Text: Pubget]

30. Kamatani, N., Hakoda, M., Otsuka, S., Yoshikawa, H., Kashiwazaki, S. Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients. J. Clin. Invest. 90: 130-135, 1992. [PubMed: 1353080, related citations] [Full Text: Journal of Clinical Investigation, Pubget]

31. Kamatani, N., Kuroshima, S., Hakoda, M., Palella, T. D., Hidaka, Y. Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation. Hum. Genet. 85: 600-604, 1990. [PubMed: 2227951, related citations] [Full Text: Pubget]

32. Kamatani, N., Kuroshima, S., Terai, C., Hidaka, Y., Palella, T. D., Nishioka, K. Detection of an amino acid substitution in the mutant enzyme for a special type of adenine phosphoribosyltransferase (APRT) deficiency by sequence-specific protein cleavage. Am. J. Hum. Genet. 45: 325-331, 1989. [PubMed: 2502918, related citations] [Full Text: Pubget]

33. Kamatani, N., Kuroshima, S., Terai, C., Kawai, K., Mikanagi, K., Nishioka, K. Selection of human cells having two different types of mutations in individual cells (genetic/artificial mutants): application to the diagnosis of the heterozygous state for a type of adenine phosphoribosyltransferase deficiency. Hum. Genet. 76: 148-152, 1987. [PubMed: 3610146, related citations] [Full Text: Pubget]

34. Kamatani, N., Kuroshima, S., Yamanaka, H., Nakashe, S., Take, H., Hakoda, M. Identification of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis. Hum. Genet. 85: 500-504, 1990. [PubMed: 2227934, related citations] [Full Text: Pubget]

35. Kamatani, N., Terai, C., Kim, S. Y., Chen, C.-L., Yamanaka, H., Hakoda, M., Totokawa, S., Kashiwazaki, S. The origin of the most common mutation of adenine phosphoribosyltransferase among Japanese goes back to a prehistoric era. Hum. Genet. 98: 596-600, 1996. [PubMed: 8882882, related citations] [Full Text: Pubget]

36. Kamatani, N., Terai, C., Kuroshima, S., Nishioka, K., Mikanagi, K. Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies. Hum. Genet. 75: 163-168, 1987. [PubMed: 3817810, related citations] [Full Text: Pubget]

37. Kelley, W. N., Levy, R. I., Rosenbloom, F. M., Henderson, J. F., Seegmiller, J. E. Adenine phosphoribosyltransferase deficiency: a previously undescribed genetic defect in man. J. Clin. Invest. 47: 2281-2289, 1968. [PubMed: 5676523, related citations] [Full Text: Journal of Clinical Investigation, Pubget]

38. Kishi, T., Kidani, K., Komazawa, Y., Sakura, N., Matsuura, R., Kobayashi, M., Tanabe, A., Hyodo, S., Kittaka, E., Sakano, T., Tanaka, Y., Kobayashi, Y., Nakamoto, T., Nakatsu, H., Moriyama, H., Hayashi, M., Nihira, H., Usui, T. Complete deficiency of adenine phosphoribosyltransferase: a report of three cases and immunologic and phagocytic investigations. Pediat. Res. 18: 30-34, 1984. [PubMed: 6701033, related citations] [Full Text: Pubget]

39. Lavinha, J., Morrison, N., Glasgow, L., Ferguson-Smith, M. A. Further evidence for the regional localization of human APRT and DIA4 on chromosome 16. (Abstract) Cytogenet. Cell Genet. 37: 517 only, 1984.

40. Laxdal, T. 2,8-Dihydroxyadenine crystalluria vs urolithiasis. (Letter) Lancet 340: 184 only, 1992. [PubMed: 1352601, related citations] [Full Text: Elsevier Science, Pubget]

41. Laxdal, T., Jonasson, T. A. Adenine phosphoribosyltransferase deficiency in Iceland. Acta Med. Scand. 224: 621-626, 1988. [PubMed: 3207073, related citations] [Full Text: Pubget]

42. Lester, S. C., LeVan, S. K., Steglich, C., DeMars, R. Expression of human genes of adenine phosphoribosyltransferase and hypoxanthine-guanine phosphoribosyltransferase after genetic transformation of mouse cells with purified human DNA. Somat. Cell Genet. 6: 241-259, 1980. [PubMed: 6994264, related citations] [Full Text: Pubget]

43. Maddocks, J. L. 2,8-Dihydroxyadenine urolithiasis. (Letter) Lancet 339: 1296 only, 1992. [PubMed: 1349689, related citations] [Full Text: Pubget]

44. Maddocks, J. L., Al-Safi, S. A. Adenine phosphoribosyltransferase deficiency: a simple diagnostic test. Clin. Sci. 75: 217-220, 1988. [PubMed: 3409638, related citations] [Full Text: Pubget]

45. Manyak, M. J., Frensilli, F. J., Miller, H. C. 2,8-Dihydroxyadenine urolithiasis: report of an adult case in the United States. J. Urol. 137: 312-314, 1987. [PubMed: 3806829, related citations] [Full Text: Pubget]

46. Marimo, B., Giannelli, F. Gene dosage effect in human trisomy 16. Nature 256: 204-206, 1975. [PubMed: 1152988, related citations] [Full Text: Pubget]

47. Menardi, C., Schneider, R., Neuschmid-Kaspar, F., Klocker, H., Hirsch-Kauffmann, M., Auer, B., Schweiger, M. Human APRT deficiency: indication for multiple origins of the most common Caucasian mutation and detection of a novel type of mutation involving intrastrand-templated repair. Hum. Mutat. 10: 251-255, 1997. [PubMed: 9298830, related citations] [Full Text: John Wiley & Sons, Inc., Pubget]

48. Mimori, A., Hidaka, Y., Wu, V. C., Tarle, S. A., Kamatani, N., Kelley, W. N., Pallela, T. D. A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects. Am. J. Hum. Genet. 48: 103-107, 1991. [PubMed: 1985452, related citations] [Full Text: Pubget]

49. Nesterova, T. B., Borodin, P. M., Zakian, S. M., Serov, O. L. Assignment of the gene for adenine phosphoribosyltransferase on the genetic map of mouse chromosome 8. Biochem. Genet. 25: 563-568, 1987. [PubMed: 3447590, related citations] [Full Text: Pubget]

50. Rappaport, H., DeMars, R. Diaminopurine-resistant mutants of cultured, diploid human fibroblasts. Genetics 75: 335-345, 1973. [PubMed: 4358687, related citations] [Full Text: HighWire Press, Pubget]

51. Sahota, A., Chen, J., Behzadian, M. A., Ravindra, R., Takeuchi, H., Stambrook, P. J., Tischfield, J. A. 2,8-Dihydroxyadenine lithiasis in a Japanese patient heterozygous at the adenine phosphoribosyltransferase locus. Am. J. Hum. Genet. 48: 983-989, 1991. [PubMed: 1673292, related citations] [Full Text: Pubget]

52. Sahota, A., Chen, J., Boyadijev, S. A., Gault, M. H., Tischfield, J. A. Missense mutation in the adenine phosphoribosyltransferase gene causing 2,8-dihydroxyadenine urolithiasis. Hum. Molec. Genet. 3: 817-818, 1994. [PubMed: 7915931, related citations] [Full Text: HighWire Press, Pubget]

53. Simmonds, H. A. 2,8-Dihydroxyadeninuria--or when is a uric acid stone not a uric acid stone? Clin. Nephrol. 12: 195-197, 1979. [PubMed: 389507, related citations] [Full Text: Pubget]

54. Simmonds, H. A., Van Acker, K. J., Sahota, A. S. 2,8-Dihydroxyadenine urolithiasis. (Letter) Lancet 339: 1295-1296, 1992. [PubMed: 1349687, related citations] [Full Text: Pubget]

55. Simon, A. E., Taylor, M. W. High-frequency mutation at the adenine phosphoribosyltransferase locus in Chinese hamster ovary cells due to deletion of the gene. Proc. Nat. Acad. Sci. 80: 810-814, 1983. [PubMed: 6572371, related citations] [Full Text: HighWire Press, Pubget]

56. Takeuchi, F., Matsuta, K., Miyamoto, T., Enomoto, S., Fujimori, S., Akaoka, I., Kamatani, N., Nishioka, K. Rapid method for the diagnosis of partial adenine phosphoribosyltransferase deficiencies causing 2,8-dihydroxyadenine urolithiasis. Hum. Genet. 71: 167-170, 1985. [PubMed: 4043967, related citations] [Full Text: Pubget]

57. Taniguchi, A., Hakoda, M., Yamanaka, H., Terai, C., Hikiji, K., Kawaguchi, R., Konishi, N., Kashiwazaki, S., Kamatani, N. A germline mutation abolishing the original stop codon of the human adenine phosphoribosyltransferase (APRT) gene leads to complete loss of the enzyme protein. Hum. Genet. 102: 197-202, 1998. [PubMed: 9521589, related citations] [Full Text: Springer, Pubget]

58. Terai, C., Hakoda, M., Yamanaka, H., Kamatani, N., Okai, M., Takahashi, F., Kashiwazaki, S. Adenine phosphoribosyltransferase deficiency identified by urinary sediment analysis: cellular and molecular confirmation. Clin. Genet. 48: 246-250, 1995. [PubMed: 8825602, related citations] [Full Text: Pubget]

59. Tischfield, J. A., Ruddle, F. H. Assignment of the gene for adenine phosphoribosyltransferase to human chromosome 16 by mouse-human somatic cell hybridization. Proc. Nat. Acad. Sci. 71: 45-49, 1974. [PubMed: 4129802, related citations] [Full Text: Pubget]

60. Van Acker, K. J., Simmonds, H. A., Potter, C., Cameron, J. S. Complete deficiency of adenine phosphoribosyltransferase: report of a family. New Eng. J. Med. 297: 127-132, 1977. [PubMed: 865583, related citations] [Full Text: Atypon, Pubget]

61. Wang, L., Ou, X., Sebesta, I., Vondrak, K., Krijt, J., Elleder, M., Poupetova, H., Ledvinova, J., Zeman, J., Simmonds, H. A., Tischfield, J. A., Sahota, A. Combined adenine phosphoribosyltransferase and N-acetylgalactosamine-6-sulfate sulfatase deficiency. Molec. Genet. Metab. 68: 78-85, 1999. [PubMed: 10479485, related citations] [Full Text: Elsevier Science, Pubget]

62. Ward, I. D., Addison, G. M. 2,8-Dihydroxyadenine urolithiasis. (Letter) Lancet 339: 1296, 1992. [PubMed: 1349690, related citations] [Full Text: Pubget]

63. Wilson, J. M., O'Toole, T. E., Argos, P., Shewach, D. S., Daddona, P. E., Kelley, W. N. Human adenine phosphoribosyltransferase: complete amino acid sequence of the erythrocyte enzyme. J. Biol. Chem. 261: 13677-13683, 1986. [PubMed: 3531209, related citations] [Full Text: HighWire Press, Pubget]

Contributors: Victor A. McKusick - updated : 1/6/2000
Victor A. McKusick - updated : 4/25/1998
Victor A. McKusick - updated : 4/1/1998
Victor A. McKusick - updated : 10/10/1997
Creation Date: Victor A. McKusick : 6/4/1986
Edit History: carol : 04/22/2011
wwang : 12/28/2009
carol : 3/24/2009
carol : 3/23/2009
ckniffin : 9/24/2008
carol : 8/27/2008
alopez : 2/3/2006
terry : 5/17/2005
carol : 3/17/2004
ckniffin : 3/12/2004
cwells : 11/10/2003
mcapotos : 11/30/2000
terry : 10/6/2000
mgross : 1/11/2000
terry : 1/6/2000
terry : 4/29/1999
carol : 11/10/1998
alopez : 5/14/1998
carol : 5/2/1998
terry : 4/25/1998
alopez : 4/1/1998
terry : 3/23/1998
terry : 3/20/1998
jenny : 10/17/1997
terry : 10/10/1997
alopez : 6/3/1997
alopez : 5/13/1997
terry : 5/6/1997
carol : 7/6/1996
mark : 6/24/1996
terry : 6/12/1996
carol : 5/18/1996
mark : 1/17/1996
mark : 1/17/1996
pfoster : 11/29/1994
mimadm : 4/14/1994
warfield : 4/6/1994
carol : 7/9/1993
carol : 2/17/1993
carol : 10/28/1992