| Project/Area Number |
08670864
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | FUKUI MEDICAL SCHOOL |
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Principal Investigator |
KIKAWA Yoshiharu DEPARTMENT OF PEDIATRICS,FUKUI MEDICAL SCHOOL,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (90143940)
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| Co-Investigator(Kenkyū-buntansha) |
INUZUKA Manabu DEPARTMENT OF BIOCHEMISTRY,FUKUI MEDICAL SCHOOL,ASSOCIATE PROFESSOR, 医学部, 助教授 (00135104)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Fructose-1,6-bisphosphatase deficiency / 960 / 961insG mutation / carrier detection / unexpected sudden infant death / Prevention / Molecular approach / ASO法 / SSCP / G-塩基の挿入 |
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| Research Abstract |
1 : Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive inherited disorder and may cause sudden unexpected infants death. Molecular analysis was performed in 13 Japanese patients with fructose-1,6-bisphosphatase (FBPase) deficiency. Four mutations responsible for FBPase deficiency were identified in 10 patients from 8 unrelated families among a total of 13 patients from 11 unrelated families. No mutation was found in the remaining 3 patients from 3 unrelated families. 960/96linsG (46% : 10 of the 22 mutant alleles], G164S (14% : 3 of the 22 alleles), A177D (4% : 1 of the 22 mutant alleles) and E30X (9% : 2 of the 22 mutant alleles). Our results indicate that 960/96linsG was associated with a preferential disease-causing alternation in the 13 Japanese patients. Accurate carrier detection in 8 families (73%) of 11 Japanese patients with FBPase deficiency is now possible.
2 : In moleuclar analysis of 10 European patients with FBPase deficiency from 10 unelated families, we found 4 kind of molecular defects in 3 among the 10 patients ; two unidentified mutations possibly leading to the failure of formation of mRNA encoding FBPase, one novel nonsense mutation E30X (10% : 2 of the 20 mutant alleles), and one known 960/961insG (5% : 1 of the 20 mutant alleles). No mutation responsible for enzyme deficiency, including the Q228X and 96lInsG mutations, was not found at genomic DNA analysis of the remaining 7 out of the 10 patients. These findings show marked heterogeneity of mutations in European patients in compared with those in Japanese patients.
3 : To prevent unexpected infant death caused by FBPase deficiency, we tried to detect carriers for FBPase deficiency with the 960/961insG mutation by SSCP method. However, this approach was found to be impractical due to the presence of polymorphism involved in the sequece surrounding the mutation.
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