Summary
A virtually complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A novel mutation of HPRT gene in a Japanese Lesch-Nyhan family has been identified using mRNA and genomic DNA from peripheral blood cells. A single nucleotide substitution of T to C in exon 3 resulted in a mis-sensemutation, CTC (Leu) to CCC (Pro), at codon 65. Utilizing anMnlI restriction site which was lost in the mutation as an indicator,a family study showed that the mother was normal not having the mutant gene. The mutation was ade novo event that had occurred in the germ cells of the mother or in the proband during the early phase of fetal development.
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Choi Y, Koo JW, Ha IS, Yamada Y, Goto H, Ogasawara N (1993): Partial hypoxanthineguanine phosphoribosyltransferase deficiency in two Korean siblings-a new mutation. Pediatr Nephrol7: 739–740
Kelley WN, Rosenbloom FM, Henderson JF, Seegmiller JE (1967): A specific enzyme defect in gout associated with overproduction of uric acid. Proc Natl Acad Sci USA57: 1735–1739
Ogasawara N, Stout JT, Goto H, Sonta S, Matsumoto A, Caskey CT (1989): Molecular analysis of a female Lesch-Nyhan patient. J Clin Invest84: 1024–1027
Sculley DG, Dawson PA, Emmerson BT, Gordon RB (1992): A review of the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency. Hum Genet90: 195–207
Seegmiller JE, Rosenbloom FM, Kelley WN 1967: Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science155: 1682–1684
yamada Y, Goto H, Suzumori K, Adachi R, Ogasawara N (1992): Molecular analysis of five idependent Japanese mutant genes responsible for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency. Hum Genet90: 379–384
Yamada Y, Goto H, Tamura S, Ogasawara N (1993): Molecular genetic study of a Japanese family with Lesch-Nyhan syndrome: a point mutation at the consensus region of RNA splicing (HPRTkelo). Jpn J Human Genet38: 413–419
Yamada Y, Goto H, Yukawa T, Akazawa H, Ogasawara N (1995a): Molecular mechanisms of the second female Lesch-Nyhan patient. Adv Exp Med Biol370: 337–340
Yamada Y, Choi Y, Kim KJ, Koo JW, Ha IS, Goto H, Ogasawara N (1995b): Hypoxanthine guanine phosphoribosyltransferase (HPRT) gene mutations in Korean families with Lesch-Nyhan syndrome. Purine Pyrimidine Metab19: 13–21 (in Japanese)
Yamada Y, Suzumori K, Tanemura M, Goto H, Ogasawara N (1996): Molecular analysis of a Japanese family with Lesch-Nyhan syndrome: Identification of mutation and prenatal diagnosis. Clin Genet50: 164–167
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Yamada, Y., Goto, H., Shiomi, M. et al. A novelde novo mutation in HPRT gene responsible for Lesch-Nyhan syndrome (HPRTosaka). Jap J Human Genet 41, 427–430 (1996). https://doi.org/10.1007/BF01876335
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DOI: https://doi.org/10.1007/BF01876335