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Triploidy is the presence of an extra haploid set of chromosomes and can exist in complete or mosaic form. The extra haploid set of chromosomes in triploid cells can be of maternal or paternal origin. Diploid/triploid mixoploidy is a unique form of triploid mosaicism that requires the aberrant segregation of entire parental genomes into distinct blastomere lineages (heterogoneic cell division) at the earliest zygotic divisions. Here we report on eight cases of diploid/triploid mixoploidy from our institution and conduct a comprehensive review of the literature. The parental origin of the extra set of chromosomes was determined in two cases; and, based on phenotypic evidence we propose the parental origin in the other cases. One case with complex mixoploidy appears to have a digynic origin in addition to the involvement of two different sperm. Of our eight cases, only one resulted in the birth of a live healthy child. The other pregnancies ended in miscarriage, elective termination of pregnancy, intrauterine fetal demise or neonatal death. A review of the literature and the results of our cases show that a preponderance of recognized cases of diploid/triploid mixoploidy has a digynic origin.

Rift Valley fever virus infection of pregnant rats results in fetal infection and death, even in dams with no signs of illness., Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women has also been associated with RVFV infection. To address how RVFV infection during pregnancy causes detrimental effects on the fetus, we developed a pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their nonpregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a previously unrecognized preference for infection, replication, and tissue damage in the placenta. In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with replication detected in the outermost syncytial layer. Our work identifies direct placental infection by RVFV as a mechanism for vertical transmission. This is the first study to show vertical transmission of RVFV with a lethal outcome in a species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.

Rift Valley fever virus (RVFV) infections in pregnant livestock are associated with high rates of fetal demise and have been linked to miscarriage in pregnant women. To address how acute RVFV infection during pregnancy causes detrimental effects on the fetus, we developed an immunocompetent pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their non-pregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a previously unrecognized preference for infection, replication, and tissue damage in the placenta. In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with replication detected in the outermost syncytial layer. Our work identifies direct placental infection by RVFV as a mechanism for vertical transmission and points to the teratogenic potential of this virus in humans. This is the first time vertical transmission of RVFV has been shown in species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.

Pediatric renal tumors (PRT) with small round blue or spindle cell morphology can be diagnostically challenging and only a limited number of immunohistochemical markers have been documented to help in the diagnosis: paired box (Pax) 2 and nerve growth factor receptor (NGFR) positivity have been demonstrated in Wilms tumor (WT) and clear cell sarcoma of the kidney (CCSK), respectively. However, the immunohistochemical expression of these markers in other PRT remains unknown. This study investigated Pax8, Pax2, and NGFR immunophenotype in a large series of PRT. Pax8 and Pax2 showed an identical staining pattern, and were expressed in all (100%) WT while most CCSK were negative. All congenital mesoblastic nephromas, metanephric stromal tumors, primitive neuroectodermal tumors, desmoplastic small round blue cell tumors, most rhabdoid tumors, and synovial sarcomas were negative for Pax8. NGFR was expressed in 96% of CCSK (diffuse expression in 91%). Only a minority of WT stained for NGFR: 16% showed expression in the blastemal and 25% in the mesenchymal components. NGFR expression was noted in synovial sarcomas (67%, with diffuse expression seen in only 1 case, 8%), rhabdoid tumors (19%), cellular congenital mesoblastic nephromas (13%) and metanephric stromal tumors (12.5%). Primitive neuroectodermal tumors and desmoplastic small round blue cell tumors were negative for NGFR. In conclusion, Pax8/Pax2 and NGFR are sensitive markers for the diagnosis of WT and CCSK, respectively. However, their specificity is limited by variable reactivity within a subset of other renal neoplasms.

Marfan syndrome results from mutations in an extracellular matrix glycoprotein, fibrillin. Previous studies have characterized approximately 6.9-kb of the estimated 10-kb fibrillin transcript. We have now completed the primary structure of fibrillin, elucidated the exon/intron organization of the gene and derived a physical map of the genetic locus. Pre-fibrillin consists of 2,871 amino acids which, excluding the signal peptide, are arranged into five structurally distinct regions. The largest of these regions comprises about 75% of the entire protein and consists of numerous repeated cysteine-rich sequences homologous to the peptide motifs of the epidermal growth factor (EGF) and transforming growth factor-beta binding protein (TGF-bp). Forty-three of the forty-six EGF-like repeats contain a calcium binding consensus sequence (EGF-CB) conceivably mediating protein-protein interactions. Fibrillin exhibits a few additional cysteine-rich modules that are apparently unique to this macromolecule and may represent evolutionary variants of the EGF-CB and TGF-bp motifs. Almost all of the cysteine-rich repeats are encoded by single exons; consequently, the fibrillin gene is relatively large (approximately 110-kb) and highly fragmented (65 exons). This study provides the first comprehensive analysis of the fibrillin gene and relevant information for the full characterization of Marfan syndrome mutations.

proposed by Sillence et a1 [1979] has become widely used and forms the basis for communica- tion among most geneticists about this heterogeneous disorder. It was recognized then that the analysis of different types was incomplete and as clinical studies have progressed [Levin et al, 1978; Rowe et al, 1981; Sillence, 19811 and as biochemical investigations have proceeded it has become clear that the classification must be extended.

A retrospective study was performed of 32 bacteremic children not receiving preadmission antibiotic therapy who had a diagnostic lumbar puncture for analysis of cerebrospinal fluid at the time of initial evaluation for an acute illness. In each instance, the CSF contained polymorphonuclear leukocytes without pleocytosis. Of these 32 bacteremic patients, 88% had a CSF differential cell count with 20% or fewer polymorphonuclear cells, and greater than 90% had glucose and protein concentration within the range of normal limits. All patients had a Gram-stained smear of CSF which revealed no organisms. In no instance was a CSF culture positive for a bacterial pathogen. In the bacteremic child not pretreated with antibiotics, cerebrospinal fluid which contains total white blood cell, glucose, and protein concentrations within limits of normal, a differential cell count with 20% or fewer polymorphonuclear leukocytes, and Gram-stained smear which reveals no organisms is not indicative of risk for bacterial meningitis.