2003 Fiscal Year Final Research Report Summary
Clinical and basic scientific investigation of spinal muscular atrophy towards the elucidation of disease mechanism and the development of therapy
| Project/Area Number |
12470173
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 of School of Medicine |
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Principal Investigator |
SAITO Kayoko Tokyo Women's Medical University, Pediatrics, Professor, 医学部, 教授 (90138834)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Yumi Tokyo Women's Medical University, Pediatrics, Assistant, 医学部, 助手 (40287339)
IIDA Eri Tokyo Women's Medical University, Pediatrics, Assistant, 医学部, 助手 (40281406)
ITO Mayuri Tokyo Women's Medical University, Pediatrics, Assistant, 医学部, 助手 (00366303)
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| Project Period (FY) |
2000 – 2003
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| Keywords | Spinal muscular atrophy / SMN gene / SERF1 gene / NAIP gene / Hybrid gene / RT-PCR / DNA sequencing / Gene conversion |
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| Research Abstract |
Spinal muscular atrophy (SMA) is an autosomal recessive disorder, classified into three types. The SMN (survival motor neuron) gene has been identified as a SMA-determining gene, designated SMNt and SMNc. Although the etiology of SMA is regarded as deletion of SMNt, the severity of clinical symptom is different among three types, and they show the same deletion of SMNt. In order to elucidate the basis of clinical variation, we analyzed the DNA and mRNA of the SMN gene in the Japanese 29 SMA patients. A large gene deletion including SMN and other genes as recognized in severe clinical type. We detected a hybrid gene, the products of gene conversion from SMNt to SMNc. Hybrid genes were found by a total nine patients, only in type II and III. We also performed sequence analysis of the cloned RT-PCR products of SMN exons 6,7 and 8. We obtained telomeric sequence of exon 7 of one patient. It suggests that sequence conversion replacing SMNc with SMNt may have occurred at mRNA level in this patient. In conclusion, deletion of the SMNt and the modifier genes made the phenotype more severe, and partial gene conversion event was the explanation for the milder phenotype.
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