Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inherited metabolic diseases resulting in urolithiasis secondary to urinary excretion of insoluble substances are rare but often present as urinary obstruction of renal insufficiency. We herein report a case of partial adenine phosphoribosyltransferase deficiency associated with 2,8-dihydroxyadenine urolithiasis. In family members the propositus and his younger brother are homozygotes for defective APRT genes, and who exhibits the type II phenotype designated APRT*J (Japanese type).
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PMID:2,8-Dihydroxyadenine urolithiasis due to partial deficit in adenine phosphoribosyltransferase: a case report. 160 69

Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is a rapid and sensitive method to identify point mutations in a given sequence of genomic DNA. We tried to apply the PCR-SSCP to the diagnosis of adenine phosphoribosyltransferase (APRT) deficiency, which is an autosomal recessive hereditary disease leading to 2,8-dihydroxyadenine urolithiasis. Genomic APRT genes, with or without mutations, were amplified and labeled simultaneously with 32P-dCTP by PCR. When run in a 6% polyacrylamide gel containing 10% glycerol, two types of mutant genes, APRT*Q0 and APRT*J, gave bands clearly distinct from those of the respective normal APRT genes. Since heterozygotes as well as homozygotes for these mutant APRT genes can be detected in 2 days, PCR-SSCP should be a valuable method in the diagnosis of APRT deficiency and in screening a large population for APRT mutant genes.
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PMID:[Detection of mutant adenine phosphoribosyltransferase genes by polymerase chain reaction-single strand conformation polymorphism analysis]. 163 17

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.
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PMID:A mutant allele common to the type I adenine phosphoribosyltransferase deficiency in Japanese subjects. 198 52

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

Adenine phosphoribosyltransferase (APRT) deficiency causing 2,8-dihydroxyadenine urolithiasis and renal failure is present at a high frequency among the Japanese but not other ethnic groups. A special type of mutant allele, designated APRT*J, with a nucleotide substitution at codon 136 from ATG (Met) to ACG (Thr) is carried by approximately 79% of all Japanese 2,8-dihydroxyadenine urolithiasis patients. We analyzed mutant alleles of 39 APRT deficient patients using a specific oligonucleotide hybridization method after in vitro amplification of a part of the genomic APRT sequence. We found that 24 had only APRT*J alleles. Determination of the haplotypes of 194 APRT alleles from control Japanese subjects and of the 48 different APRT*J alleles indicated that normal alleles occur in four major haplotypes, whereas all APRT*J alleles occur in only two. These results suggest that all APRT*J alleles have a single origin and that this mutant sequence has been maintained for a long period, as calculated from the frequency of the recombinant alleles.
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PMID:Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation. 222 51

Patients with 2,8-dihydroxyadenine urolithiasis are either completely or partially deficient in adenine phosphoribosyltransferase activities. Patients with partial enzyme deficiencies, all of whom have been found among Japanese, are homozygotes having a unique mutant adenine phosphoribosyltransferase gene (APRT*J) in double dose (Japanese type deficiency). We have established B-cell lines from heterozygotes and homozygotes of complete and Japanese type adenine phosphoribosyltransferase deficiencies as well as normal individuals. Characterization of the cell lines indicated that all homozygous cells were deficient in adenine phosphoribosyltransferase function while all heterozygous and normal cells had functional adenine phosphoribosyltransferase.
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PMID:Establishment and characterization of B cell lines from individuals with various types of adenine phosphoribosyltransferase deficiencies. 348 62

2,8-Dihydroxyadenine urolithiasis associated with partial deficiencies of adenine phosphoribosyltransferase (APRT) has been found only among Japanese families. All Caucasian patients with the same lithiasis are completely deficient in this enzyme. Partially purified APRT from one of the Japanese families with the lithiasis associated with a partial deficiency of APRT had a reduced affinity for 5-phosphoribosyl-1-pyrophosphate (PRPP). In the present investigations, we have shown that this characteristic is common in mutant enzymes from all the four separate Japanese urolithiasis families associated with partial APRT deficiencies so far tested. The mutant enzymes also had several other characteristics in common including increased resistance to heat in the absence of PRPP and reduced sensitivity to the stabilizing effect of PRPP. These data suggest that these families have a common mutant allele (APRT*J) at the APRT gene locus.
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PMID:Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2,8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies. 387 64

We analyzed DNA from six Japanese patients with adenine phosphoribosyltransferase (APRT) deficiency who developed 2,8-dihydroxyadenine (DHA) urolithiasis. These six patients were selected for DNA analysis since they were expected to possess allele(s) with mutations other than two known abnormalities, i.e. a missense mutation at codon 136 (APRT*J allele) and a nonsense mutation at codon 98. In three of the six patients an insert of four bases CCGA was detected in exon 3 by sequencing clones obtained from the genomic DNA. In two of the three patients, both of the two alleles had this mutation (homozygotes) while the other patient had the APRT*J allele in addition to the allele with the 4-base insertion. To search for mutations other than the above three defined germline mutations, we amplified a genomic DNA segment including all the 5 exons of the APRT gene by PCR and cloned it into a plasmid. After selecting recombinant plasmids containing neither of the three defined mutations, we sequenced the entire APRT exons and introns. Abnormalities were found in neither the coding regions nor the exon-intron junctions. Disease-related mutations in these mutant alleles may exist in either 5' or 3' flanking sequences and remain to be elucidated.
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PMID:Detection of the three common mutations of adeninephosphoribosyltransferase deficiency among Japanese. 775 7

We report a case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis. Polymerase chain reaction-single strand conformation polymorphism analysis demonstrated that APRT*J and APRT*Q0 alleles from the father and mother, respectively, had been transmitted to the patient. We also reviewed the literature regarding Japanese patients with 2,8-dihydroxyadenine urolithiasis. There seemed to be little difference in clinical course between type 2 homozygotes and compound heterozygotes. However, hemolysate APRT activities of compound heterozygotes were lower than those of type 2 homozygotes.
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PMID:A case of a compound heterozygote for adenine phosphoribosyltransferase deficiency (APRT*J/APRT*Q0) leading to 2,8-dihydroxyadenine urolithiasis: review of the reported cases with 2,8-dihydroxyadenine stones in Japan. 845 50

Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis is a rapid and sensitive method used to identify point mutations in a given sequence of genomic DNA. We applied this method to the diagnosis of adenine phosphoribosyltransferase (APRT) deficiency, which is an autosomal recessive hereditary disease leading to 2,8-dihydroxyadenine urolithiasis. Genomic APRT genes were amplified and labeled simultaneously with [alpha-32P]dCTP (cytidine triphosphate) by PCR. When run in a 6% polyacrylamide gel containing 10% glycerol, two types of mutant genes-APRT*QO and APRT*J-gave bands clearly distinct from those of the equivalent normal APRT genes. Using this method we diagnosed both homozygotes and heterozygotes for defective APRT genes. On screening 80 Japanese individuals for polymorphism or mutations by PCR-SSCP we did not find any alterations leading to a false positive diagnosis. These findings suggest that PCR-SSCP, in addition to being rapid and sensitive, is a useful diagnostic method which is highly specific in detecting mutant APRT genes in the Japanese population.
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PMID:Application of polymerase chain reaction-single strand conformation polymorphism analysis to the diagnosis and screening of adenine phosphoribosyltransferase deficiency. 850 53


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