2005 Fiscal Year Final Research Report Summary
Basic Research of pre-implantation genetic diagnosis of hypophosphatasia
| Project/Area Number |
15591788
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Hyogo College of Medicine |
|---|
Principal Investigator |
HORIUCHU Isao Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (70340974)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SAWAI Hideaki Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (80215904)
KOMORI Shinji Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60195865)
AKATANI Akiko (HASEGAWA Akiko) Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (50212402)
KOYAMA Koji Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (00068496)
|
|---|
| Project Period (FY) |
2003 – 2005
|
| Keywords | hypophosphatasia / pre-implantation diagnosis / diagnosis of embryo / prenatal diagnosis / tissue non-specific alkaline phosphatase |
|---|
| Research Abstract |
Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and deficiency of tissue nonspecific alkaline phosphatase (TNSALP) activity. This disorder is caused by various mutations in the TNSALP gene. We reported hypophosphatasia in two siblings, both of them severely affected by the perinatal (lethal) type. We diagnosed the first infant by clinical and radiologic manifestations, and laboratory findings. Laboratory findings were characterized by deficiency of serum alkaline phosphatase. Both parents and the second infant were then analyzed by molecular techniques. The radiograph of the first infant showed severe hypomineralization of the skeleton. Molecular analysis of the second infant showed that this condition was caused by a homozygous single T nucleotide deletion at cDNA number 1559 (1559delT). Both parents were heterozygous carriers for this mutation, although they were not consanguineous. This mutation has been frequently found in Japanese hypophosp
… More
hatasia patients, but this is the first observation of a homozygous deletion. This report shows that homozygosity for the 1559delT mutation of the TNSALP gene results in a severe lethal phenotype. To perform pre-implantation diagnosis first we set up a mouse system for pre-implantation diagnosis. We pick up a blastomeret of mouse embryo, then one blastomere was subjected for sexing and the remaining blastomere was transferred in utero. We calculated the accuracy of the sexing, when the futus of mice were born. The accuracy was more than 90%. Next we set up single cells (leukocyte) amplification system from the carrier individuals of hypophosphatasia. The amplification was successful in more than 90% cells. However the problem of allele drop out still remains. Overall approximately half of the samples were successful for both allele amplification. However if the normal allele is amplified, the individual is normal or carrier, then the clinically. Then our strategy should be useful for pre-implantation diagnosis of hypophosphatasia. Less
|
