| Project/Area Number |
04670615
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | OSAKA CITY UNIVERSITY |
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Principal Investigator |
ISSHIKI Gen Osaka City University Medical School Department of Pediatrics, Professor, 医学部, 教授 (80046995)
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| Co-Investigator(Kenkyū-buntansha) |
OKANO Yoshiyuki Osaka City Univ.Med.Sch.Dept.of Ped.Assistant, 医学部, 助手 (60231213)
TANAKA Akemi Osaka City Univ.Med.Sch.Dept.of Ped.Lecturer, 医学部, 講師 (30145776)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Galactosemia / Inherited metabolic disease / Calactose-1-phosphate uridy, 1 transferase / Mutation / Autosomal Recessive / Gene Expression / 先天性代謝異常症 |
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| Research Abstract |
Classic deficiency galactosemia is an autosomal recessive genetic disorder caused by a deficiency of galactose-1-phosphate uridyl transferase (GALT).We characterized three novel mutations of the GALT gene, and idenified N314D and R333W mutations, previously found in Caucasians from seven Japanese families with GALT deficiency.One novel missense mutation was a G to A transition in exon 8, resulting in the substitution of arginine by histidine at the codon 231 (R231H).GALT activity of the R231H mutant construct was reduced to 15% of normal controls in a COS cell expression system.The second missense mutation was a A to G transition in exon 5, resulting in substitution of methionine by valine at the codon 142 (M142V).The third was a splicing matation, an A to G transition at the 38th nucleotide in exon 3 (318A*G), resulting in a 38 bp deletion in the GALT cDNA by activating a cryptic splice acceptor site. These three mutations were not found in Caucasians.In seven Japanese families (14 alleles for classic form and one allele for Duarte variant) with GALT deficiency, R231H and 318A * G were found only on both alleles of the proband. M142V was found on two alleles with compound heterozygote in two families. N314D and R333W were found on one allele each.Q188R was prevalent in the United States but not in Japanese patients. N314D was associated with the Duarte variant in Japanese as well as in the United States.We identified the mutation in 8 of 15 alleles (53%).We speculate that the N314D GALT mutation encoding the Duarte variant arose before Asian and Caucasian people diverged and that classic galactosemia mutations arose and/or accumulated after Asian and Caucasian people diverged.
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