-
The Journal of Biological Chemistry Oct 2007A palmitate linked to the inositol in glycosylphosphatidylinositol (GPI) is removed in the endoplasmic reticulum immediately after the conjugation of GPI with proteins...
A palmitate linked to the inositol in glycosylphosphatidylinositol (GPI) is removed in the endoplasmic reticulum immediately after the conjugation of GPI with proteins in most cells. Previously, we identified PGAP1 (post GPI attachment to proteins 1) as a GPI inositoldeacylase that removes the palmitate from inositol. A defect in PGAP1 caused a delay in the transport of GPI-anchored proteins (GPI-APs) from the endoplasmic reticulum to the cell surface in Chinese hamster ovary cells, although the cell-surface expression of GPI-APs in the steady state was normal. Nevertheless, in most cells, GPI-APs undergo deacylation. To elucidate the biological significance of PGAP1 in vivo, we established PGAP1 knock-out mice. Most PGAP1 knock-out mice showed otocephaly, a developmental defect, and died right after birth. However, some survived with growth retardation. Male knock-out mice showed severely reduced fertility despite the capability of ejaculation. Their spermatozoa were normal in number, motility, and ability to ascend the uterus, but were unable to go into the oviduct. In vitro, PGAP1-deficient spermatozoa showed weak attachment to the zona pellucida and a severely diminished rate of fertilization. Therefore, an extra acyl chain in GPI anchors caused severe deleterious effects to development and sperm function.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Endoplasmic Reticulum; Female; Glycosylphosphatidylinositols; Heterozygote; Infertility, Male; Male; Membrane Proteins; Mice; Mice, Knockout; Oviducts; Palmitic Acid; Phosphoric Monoester Hydrolases; Protein Processing, Post-Translational; Skull; Sperm Motility; Sperm-Ovum Interactions; Spermatozoa; Uterus; Zona Pellucida
PubMed: 17711852
DOI: 10.1074/jbc.M705601200 -
Journal of the Chinese Medical... Jul 2007Otocephaly is a rare lethal syndrome of microstomia, aglossia, agnathia, and synotia. This male infant was born to a 19-year-old, gravida 1, para 0, woman who received...
Otocephaly is a rare lethal syndrome of microstomia, aglossia, agnathia, and synotia. This male infant was born to a 19-year-old, gravida 1, para 0, woman who received routine prenatal check-up. Polyhydramnios, low-lying ears, and proboscis were noted by sonography at 29 weeks of gestation. Amniocentesis showed a normal karyotype of 46, XY. Premature rupture of membranes and preterm labor were noted at 32 weeks of gestation. A male infant was delivered preterm and died shortly after birth. The infant showed midline proboscis and absence of mandible. The simple, soft ears were extremely low-set and were near the midline of the neck. Otocephaly is regarded as the most severe form of first arch anomalies. Prenatal diagnosis should be dependent on ultrasound analysis. In the face of polyhydramnios, otocephaly is one of the possible fetal anomalies.
Topics: Abnormalities, Multiple; Adult; Ear; Female; Humans; Infant, Newborn; Male; Microstomia; Pregnancy; Syndrome; Ultrasonography, Prenatal
PubMed: 17631468
DOI: 10.1016/S1726-4901(07)70009-6 -
Prenatal Diagnosis Jul 2007
Topics: Adult; Airway Obstruction; Craniofacial Abnormalities; Female; Humans; Imaging, Three-Dimensional; Infant, Newborn; Infant, Premature; Male; Mandible; Neonatology; Placental Circulation; Pregnancy; Ultrasonography, Prenatal
PubMed: 17497748
DOI: 10.1002/pd.1754 -
Prenatal Diagnosis May 2007
Topics: Abortion, Eugenic; Adult; Craniofacial Abnormalities; Diagnosis, Differential; Female; Humans; Mandible; Pregnancy; Ultrasonography, Prenatal
PubMed: 17471605
DOI: 10.1002/pd.1709 -
Fetal and Pediatric Pathology 2006Otocephaly, characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with...
Otocephaly, characterized by mandibular hypoplasia or agnathia, ventromedial auricular malposition (melotia) and/or auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia, is an extremely rare anomalad, identified in less than 1 in 70,000 births. The malformation spectrum is essentially lethal, because of ventilatory problems, and represents a developmental field defect of blastogenesis primarily affecting thefirst branchial arch derivatives. Holoprosencephaly is the most commonly identified association, but skeletal, genitourinary, and cardiovascular anomalies, and situs inversus have been reported. Polyhydramnios may be the presenting feature, but prenatal diagnosis has been uncommon. We present five new cases of otocephaly, the largest published series to date, with comprehensive review of the literature and an update of research in the etiopathogenesis of this malformation complex. One of our cases had situs inversus, and two presented with unexplained polyhydramnios. Otocephaly, while quite rare, should be considered in the differential diagnosis of this gestational complication.
Topics: Abnormalities, Multiple; Craniofacial Abnormalities; Ear; Female; Humans; Infant, Newborn; Male; Mandible; Microstomia; Polyhydramnios; Pregnancy; Tongue
PubMed: 17438667
DOI: 10.1080/15513810601123417 -
Ultrasound in Obstetrics & Gynecology :... Apr 2007
Topics: Abnormalities, Multiple; Abortion, Eugenic; Craniofacial Abnormalities; Female; Humans; Magnetic Resonance Imaging; Pregnancy; Pregnancy Trimester, Second; Ultrasonography, Prenatal
PubMed: 17330829
DOI: 10.1002/uog.3956 -
Prenatal Diagnosis Feb 2007The dysgnathia complex (agnathia-otocephaly) (AO) is a lethal malformation that consists of congenital absence of the lower jaw with union or close approximation of the...
The dysgnathia complex (agnathia-otocephaly) (AO) is a lethal malformation that consists of congenital absence of the lower jaw with union or close approximation of the lower ears on the front of the neck, microstomia, and hypoglossia. We present a novel case of agnathia-otocephaly with associated organomegaly and the use of postmortem 3-D computed tomographic rendering.
Topics: Abnormalities, Multiple; Adult; Ear; Fatal Outcome; Female; Fetus; Gestational Age; Humans; Image Processing, Computer-Assisted; Mandible; Maxillofacial Abnormalities; Polyhydramnios; Pregnancy; Syndrome; Tomography, X-Ray Computed
PubMed: 17152114
DOI: 10.1002/pd.1626 -
Genetic Counseling (Geneva, Switzerland) 2006Otocephaly is a rare lethal malformation of the first and second branchial arches. We report two infants with otocephaly and failed resuscitation. Both infants had...
Otocephaly is a rare lethal malformation of the first and second branchial arches. We report two infants with otocephaly and failed resuscitation. Both infants had pulmonary malformations: pulmonary hypoplasia and two-lobed right lung. We report these rare associations with a brief review of the literature.
Topics: Abnormalities, Multiple; Central Nervous System; Ear; Fatal Outcome; Heart Defects, Congenital; Humans; Infant, Newborn; Lung; Male; Mandible; Urogenital Abnormalities
PubMed: 16970034
DOI: No ID Found -
Congenital Anomalies Mar 2006Reconstructed micro computed tomography (Micro-CT, micro-CT) images have revealed the detailed three-dimensional structure of the cranium of human fetal congenital...
Reconstructed micro computed tomography (Micro-CT, micro-CT) images have revealed the detailed three-dimensional structure of the cranium of human fetal congenital anomalies for the first time. The objects were a head and a cervix of female autosite and a parasite consisting of only a head conjoined to the scapular region of the autosite of an asymmetric double malformation (asymmetric conjoined twins, heteropagus twinning) at a gestational age of 8 months. The cranium of the autosite was normal, but that of the parasite was characterized by otocephaly (agnathia, synotia, and monorhina) and almost all the cranial bones were of an abnormal shape. It is suggested that a part of occipital bone (the basioccipital and exoccipital bones), the vomer and cribriform plate were absent and this resulted in the fusion and overlapping of bilateral temporal and craniofacial bones that should have been adjacent to them. This resulted in a reformation and relocation of most of the cranial bones. Micro-CT is a useful tool to visualize the detailed bone structure which has not been clarified by the conventional dissection methods and other imaging technologies and is a powerful instrument for studying congenital anomalies.
Topics: Bone and Bones; Craniofacial Abnormalities; Female; Fetus; Humans; Imaging, Three-Dimensional; Skull; Tomography, X-Ray Computed; Twins, Conjoined
PubMed: 16643593
DOI: 10.1111/j.1741-4520.2006.00095.x -
The Veterinary Record Apr 2006
Topics: Abnormalities, Multiple; Animals; Breeding; Diagnosis, Differential; Dog Diseases; Dogs; Holoprosencephaly; Stillbirth
PubMed: 16617045
DOI: 10.1136/vr.158.15.518