Abstract
79% of all the Japanese patients with 2,8-dihydroxyadenine urolithiasis have been only partially deficient in APRT and they synthesize mutant enzyme with common altered properties (Japanese-type APRT deficiency). Based on various pieces of evidence, we have predicted that the Japanese-type patients have unique mutant gene (APRT*J) deriving from a common ancestor. Recently, Hidaka et al. identified a nucleotide substitution in exon 5 in a Japanese-type APRT deficient patient. This nucleotide substitution changes the predicted amono-acid sequence from Met to Thr at position 136. We have devised a method by which the change of Met at position 136 to another amino-acid is specifically identified. This method uses BrCN to cleave protein at Met residue and sequence-specific antisera against the probable PRPP-binding site of human APRT. Using this method, we have shown that separate families with the Japanese-type APRT deficiency exclusively synthesize methionine-free APRT. Along with other data such as RFLP of APRT gene among the patients, these data provide evidence at the molecular level for our previously presented hypothesis that the Japanese-type APRT deficiency patients are homozygotes having a unique disease-causing gene APRT*J deriving from a common ancestor gene created in an ancestor of Japanese. Explanation for the expansion of this disease-causing gene among Japanese will be presented.
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Kamatani, N., Kuroshima, S., Kawai, K. et al. 70 EVIDENCE AND EXPLANATION FOR THE PRESENCE OF A COMMON ANCESTOR DISEASE-CAUSING GENE FOR THE JAPANESE-TYPE APRT DEFICIENCY. Pediatr Res 24, 122 (1988). https://doi.org/10.1203/00006450-198807000-00094
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DOI: https://doi.org/10.1203/00006450-198807000-00094