Prenatal diagnosis and genetic analysis of type I and type II thanatophoric dysplasia
Journal
Prenatal Diagnosis
Journal Volume
21
Journal Issue
2
Pages
89-95
Date Issued
2001
Author(s)
Abstract
Thanatophoric dysplasia (TD) is one of the most common neonatal lethal skeletal dysplasias. Prenatal sonographic and molecular genetic diagnoses of three cases of TD type I (TD1) and one case of TD type II (TD2) are presented here. Two fetuses of TD1 were characterized by polyhydramnios, macrocephaly, short limbs, a narrow thoracic cage and curved short femora, but without a cloverleaf skull at 27 and 31 weeks' gestation, respectively. The third fetus with TD1 was, however, not associated with macrocephaly, polyhydramnios, chest narrowing and severe femoral bowing on prenatal ultrasound at 18 weeks' gestation. The TD2 fetus was characterized by polyhydramnios, short limbs, a narrow thoracic cage, straight short femora, hydrocephalus and a cloverleaf skull at 24 weeks' gestation. Three-dimensional ultrasound was able to enhance the visualization of thickened, redundant skin folds and craniofacial and limb deformities associated with TD. Molecular analysis of the fibroblast growth factor receptor 3 (FGFR3) gene by restriction enzyme digestion analysis and direct sequencing using cultured amniotic fluid cells or cord blood cells revealed a missense mutation of 742C→T (Arg248Cys) in all cases with TD1 and a missense mutation of 1948A→G (Lys650Glu) in the case with TD2. The present report shows that adjunctive applications of molecular genetic analysis of the FGFR3 gene and three-dimensional ultrasound are useful for prenatal diagnosis of TD. Copyright ? 2001 John Wiley & Sons, Ltd.
Subjects
FGFR3 gene; Gene mutation; Prenatal diagnosis; Thanatophoric dysplasia; Three-dimensional ultrasound
SDGs
Other Subjects
fibroblast growth factor receptor; fibroblast growth factor receptor 3; unclassified drug; article; case report; clinical feature; diagnostic value; disease association; disease classification; echography; fetus; genetic analysis; human; missense mutation; prenatal diagnosis; priority journal; thanatophoric dwarfism; three dimensional imaging; Adult; DNA Restriction Enzymes; Female; Gestational Age; Humans; Mutation; Polymerase Chain Reaction; Pregnancy; Prenatal Diagnosis; Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor; Thanatophoric Dysplasia; Ultrasonography, Prenatal
Type
journal article