1993 Fiscal Year Final Research Report Summary
DNA Diagnosis of Non-ketotic Hyperglycinemia
| Project/Area Number |
03404033
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TADA Keiya TOHOKU UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF PEDIATRICS, PROFESSOR, 医学部, 教授 (20046907)
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| Co-Investigator(Kenkyū-buntansha) |
KURE Shigeo TOHOKU UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF BIOCHEMICAL GENETICS, INSTR, 医学部, 助手 (70211191)
OHURA Toshihiro TOHOKU UNIVERSITY HOSPITAL, DEPARTMENT OF PEDIATRICS, ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (10176828)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Nonketotic Hyperglycinemia / DNA Diagnosis / Glycine Cleavage System / Prenatal diagnosis |
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| Research Abstract |
Nonketotic hyperglycinemia (NKH) is a well-recognized metabolic cause of life-threatening illness in the neonate. The foundamental defect is in the glycine cleavage system (GCS), which consists of four protein components. Our study revealed that the majority of NKH patients had a specific defect in P-protein (glycine decarboxylase). GCS is specially expressed in liver, kidney and brain. Liver biopsy is, therefore, necessary for the enzymatic diagnosis of NKH.This study was carried out to establish DNA diagnosis of NKH.structual analyzes of P-protein mRNA from the patients with NKH revealed molecular lesions such as point mutations, three-base deletion or one-base deletion resulting in frame shift. Above all, S564I mutation (an amino acid alternation from Ser^<564> to Ile^<564>) was found to be a common mutation in Finnish patients with NKH.
We developed a modified PCR method to detect S564I mutation rapidly and easily. One nucleotide in each forward and reverse primer was modified to produce recognition sites for restriction enzymes, Rsa I and Ssp I in the PCR products. With this method, we could diagnosis homozygotes and heterozygotes of S564I mutation easily using dried blood on filter paper. Prenatal diagnosis also was feasible by this method using choriomic villi obtained between 8th and 16th weeks of gestation.
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