Clinical, Epidemiological and Molecular Genetical Research for Spinal Muscular Atrophy
| Project/Area Number |
10670762
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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 | TOKYO WOMEN'S MEDICAL UNIVERSITY |
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Principal Investigator |
SAITO Kayoko Tokyo Women's Medical University, Dept. of Pediatrics, Professor, 医学部, 教授 (90138834)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAIWA Yumi Tokyo Women's Medical University of Pediatrics, Assistant, 医学部, 助手 (40287339)
IKEYA Kiyoko Tokyo Women's Medical University of Pediatrics, Assistant Professor, 医学部, 講師 (70151313)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | spinal muscular artophy / clinicla classificaion / gene analysis / SMN gene / NAIP gene / gene deletion / modifying gene / clinical severity / 脊椎性筋萎縮症 / 疫学的検討 / 臨床型と遺伝子型 / DNAとmRNA / 培養骨格筋細胞 |
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| Research Abstract |
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by mutation of the survival motor neuron (SMN) gene. We conducted a molecular genetic analysis of SMA patients and compared clinical severity with deletions of the SMNt and neuronal apoptosis inhibitory protein (NAIP) genes, and C212 and C272 microsatellite markers. We analyzed the SMN and NAIP genes in 89 SMA families ; 30 type I, 29 type II and 30 type III. Using the multi-copy microsatellite C212 and C272 markers, we performed haplotype analysis in 41 familes ; 15 type I, 15 type II and 11 type III. We defined 0-2 copies/ 2 chromosomes as a deletion of he H4F5 gene.
Seventy-eight cases (87.6%) showed deletion of both genes or only the SMN gene. A significantly higher proportion of type I patients had deletion of both genes (p<0.05). Cases who had deletion of both the SMN and NAIP genes showed significantly earlier onset of disease. There were six sibling pairs in our subjects. Disease severity in each sibling was comparable, but two sibling pairs showed different disease severity. Five type I cases had a broad deletion that spanned the H4F5, SMN and NAIP genes. A significantly higher proportion of type I subjects had this deletion.
Twenty-four of 4l (58.5%) showed C272 deletion or C212 and C272 deletion in addition to deletion of the SMN gene. We determined the number of C212 alleles present on their chromosomes by haplotype analysis. A reduction of C212 alleles was found in 48% of type I (2 copies) and in 60-80% of type II and III (3 copies). A total of 60% of the control subjects showed 4 copies. These results suggested that type I patients had homozygous deletion of C212 and type II and III patiensts had deletion of C212 in one chromosome, which means compound heterozygosity.
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Report
(3 results)
Research Products
(21 results)
