| Project/Area Number |
15591164
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
SAWAI Hideaki Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (80215904)
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| Co-Investigator(Kenkyū-buntansha) |
KOMORI Shinji Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60195865)
KOYAMA Koji Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (00068496)
TSUBAMOTO Hiroshi Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (80340975)
KONDO Nobuyuki Hyogo College of Medicine, Faculty of Medicine, Assistant Professor, 医学部, 講師 (70252682)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | osteochondrodysplasias / FGFR3 / thanatophoric dysplasia / PCR / hypochondroplasia / hypochondroplasia |
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| Research Abstract |
Thanatophoric dysplasia (TD), the most common neonatal lethal skeletal dysplasia, affects one out of 20,000 live births. A sporadic mutation causing a Lys650Glu change in the tyrosine kinase domain of FGFR3 was found in 2 of 2 individuals with TD type II. Of 20 individuals with a second type of TD, 15 had a mutation causing an Arg248Cys change and 5 had a Tyr373Cys substitution, both in the extracellular region of the protein.
Hypochondroplasia is an autosomal dominant skeletal dysplasia expressing postnatal onset of short stature with mild rhizomelic shortening of the limbs. This manifestation leads to restricted prenatal diagnosis of the disorder. We report here on a sporadic case of a hypochondroplastic baby, whose prenatal sonographic measurements were serially recorded from 19 weeks of gestation. Mild shortening of the limbs became manifest after 26 weeks of gestation. Biparietal diameter was within the normal range throughout gestation. Both parents were of average stature. A tentative diagnosis of a nonlethal short-limb skeletal dysplasia was made. At birth, the clinical manifestations of the neonate were not characteristic, but the radiographic features raised the possibility of hypochondroplasia. Molecular analyses revealed a C to G mutation at nucleotide 1659 of the fibroblast growth factor receptor 3 (FGFR3) gene, a common mutation in hypochondroplasia.
Osteochondrodysplasias similar to TD by radiological examination was examined by genetic testing. We have analyzed FGFR3 gene using denaturing high performance liquid chromatography (DHPLC). The mutation was absent from the two individuals similar phenotype to TD I. These individuals are fetuses aborted in the early in pregnancy. Then definite diagnosis by radiological findings only was not possible. We did not find any mutation in FGFR3 gene. We could not make a diagnosis of these individuals.
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