| Project/Area Number |
02671047
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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 |
Human genetics
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| Research Institution | Kumamoto University |
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Principal Investigator |
ENDO Fumio Kumamoto University, Pediatrics, Lecturer, 医学部附属病院, 講師 (00176801)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | peptidase D / prolidase / inborn errors of metabolism / gene analysis / amino acid metabolism / autosomal recessive / プリダ-ゼ / 筋ジストロフィ- / 遺伝子 / 筋緊張型筋ジストロフィ- |
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| Research Abstract |
Peptidase D (prolidase) deficiency is a rare autosomal recessive disorder characterized by various skin lesions, mental retardation, and other symptom. Peptidase D (EC 3.4.13.9) is a kind of oligopeptidases which hydrolysis imidopeptides and releases carboxyl terminal proline from the substrate peptides. We have isolated the enzyme from human blood and cloned the CDNA for human peptidase D. Then we have determined the primary structure of the enzyme, the structure of the gene and the localization of the gene.
We carried out the gene analysis of the patient with the disease. In a Japanese family with two sisters with the-disease, we found 192base pairs (bp) deflection in MRNA from cultured cells. We cloned the gene fragment which covered the deletion mutation from the patients and determined the nucleotide sequences. It was demonstrated that approximately 759 bp sequence was deleted in the gene from the patients. In the case from Belgium (originally from Meddle East), we found a point mutation (A to G at nucleotide 826) which resulted in an amino acid substitution (Asp-Asn). Expression analysis of the mutant CDNA revealed that the inactive synthesized from the CDNA. The same mutation was found in the other patient who came from Middle East. Thus the point mutation might be originated from the Middle East.
In addition we determined the nucleotide sequences surrounding the intron-exon junctions. These studies make us possible to amplify the all exons for gene analysis of this disease.
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