Abstract Huntingtin-interacting protein 1-related (Hip1r) was originally identified due to its homology to Huntingtin-interacting protein 1, which contributes to the development of Huntington's disease (HD). We studied the expression of the mouse Hip1r (mHip1r) gene in the mouse head by in situ hybridization. In early embryogenesis at embryonic day (E) 13, mHip1r expression was especially prominent in the olfactory epithelium, cerebral cortex layer 1, cortical plate, and dentate gyrus. During later development from E15 to E17, strong expression of mHip1r transcripts continued to be observed in the olfactory epithelium, cortical plate, and dentate gyrus. Furthermore, not only the subplate and subventricular zone of the cortex, but also secretory glands, such as the nasal gland and the submandibular gland, were mHip1r-positive. Other positive tissues included the retinal ganglion cells, vomeronasal organ, trigeminal ganglion, and the developing molar tooth. In the adult mouse brain, similar expression patterns were observed in the cerebral cortex layers and other brain regions except the cerebellum. Additionally, by using an antibody against mHip1r, we confirmed these expression patterns at the protein level. Specific expression of mHip1r in the embryonic brain and secretory glands suggests a possible role for Hip1r in normal development and in the pathology of HD.
Abstract Thiamazole, an anti-hyperthyroidism agent, was administered orally to pregnant cynomolgus monkeys at doses of 2.0 and 3.5 mg/kg per day from GD 120 to GD 150 to investigate effects on behavioral development of their infants. Swelling of the throat region due to enlargement of the thyroid glands was observed at birth in thiamazole-treated infants, and it returned to normal around postnatal day (PND) 30. At necropsy of infants at 12 months of age, thyroidal weight in the thiamazole groups was increased. This finding suggested the likelihood that administration of thiamazole to maternal animals during the late gestational period induced thyroid goiter in fetal/infant monkeys through placental transfer of thiamazole. No clear changes were noted in thyroid histopathology or serum thyroid hormone levels in maternal animals or infants, but goiter formation might have been indicative of exposure to high thyroid stimulating hormone (TSH) and low T3 or T4 in utero from maternal treatment with thiamazole. Age-related changes were observed in the control in behavioral development tests, while infants at 3.5 mg/kg showed no age-related decrease in contact behavior and no increase in exploratory activity on PND 90 or PND 170. In addition, the number of eye contacts between PND 210 and PND 240 was less frequent. This indicated that maternal exposure to thiamazole induced mental retardation-like behaviors in infants. Thiamazole may directly inhibit thyroid hormone synthesis in the fetus by placental transfer. From these results, it was speculated that oral administration of thiamazole to maternal animals during the late gestational period induced retardation of behavioral development in their infants.
Abstract Oral-facial-digital syndrome type 1 (OFD1; MIM 311200) is characterized by multiple anomalies of the oral cavity, face and digits. We report a family with OFD1, where two female siblings and their mother shared the same mutation of the responsible gene (OFD1) c.1193_1196delAATC. Phenotypic variability was observed among them; the mother showed minimal features of OFD1, whereas her two daughters showed partial features and the full spectrum of OFD1, respectively. Thus, OFD1 was suspected only after a health check-up during pregnancy of the second patient showing fetal brain anomaly and maternal polycystic kidney. For these reasons, there was a delay in the recognition of OFD1 in this family. Patients with OFD1 show phenotypic variability, which poses challenges for genetic counseling.
Abstract Chondrodysplasia punctata brachytelephalangic type is a common subset of a heterogeneous group of chondrodysplasia punctata. Most affected children generally do not have significant physical disabilities; however, a small number of patients are at risk of cervical canal stenosis with cervical cord compression leading to serious morbidity and early mortality. Very little is known about the in utero manifestation of severe complications. We report an affected child in whom the Binder phenotype was found on antenatal ultrasound and cervical spinal cord compression on fetal magnetic resonance imaging. Prenatal diagnosis of chondrodysplasia punctata brachytelephalangic type and its complications are beneficial for timely, prompt medical intervention.
Abstract Diastematomyelia is a rare form of spinal dysraphism. Here the spinal cord was split into two with a bony or cartilaginous spur, resulting in formation of two hemicords. The prenatal diagnosis of diastematomyelia is possible with ultrasonography. The unique finding is the appearance of echogenic focus within the spinal canal. This condition may not have any clinical sign during prenatal and early years of life but as the child grows, serious neurologic manifestations may occur, commonly termed the “tethered cord syndrome”. Here, we report a case of diastematomyelia in which a careful antenatal imaging was performed and postnatal pathologic examination confirmed the diagnosis.
Abstract Cherubism is a rare genetic disorder characterized by progressive facial deformity caused by non-neoplastic bone lesions in the mandible and/or the maxilla. Src homology-3 binding protein 2 gene (SH3BP2) has been found to be the responsible gene, with alterations in six amino acids noted in patients with this condition. Recently, mutations in this domain have been found to cause stabilization of SH3BP2 by uncoupling with tankyrase. In this study, we identified a new 2-bp mutation that led to a recurrent amino acid change in a sporadic case of cherubism. Our findings indicate that it is important to understand the pattern of progress in typical cherubism.
Abstract Anomalies of the umbilical venous system are perplexing essentially due to dissection errors and vascular connection delineation failure. Continuation of umbilical vein into the extra-hepatic portal vein is classified as group IV umbilical vein anomaly and involves the vitelline vein or its remnants. Despite this categorization most examiners ascribe fetal extra hepatic abdominal vascular abnormality as an umbilical vein anomaly. Since these anomalies involve vitelline vein, the term “umbilical vein anomaly” is inappropriate and should be referred to as “vitelline vein abnormalities”. Vitelline vein abnormalities are exceedingly rare and to the best of our knowledge only three cases have been reported prenatally. We report three cases presenting with intrauterine fetal demise and on perinatal autopsy demonstrating aneurysmally dilated group IV umbilical vein anomaly. Review of the literature, embryological basis and clinical implications of persistent vitelline vein and its varix are discussed.