Triploid pregnancies: genetic and clinical features of 158 cases.

OBJECTIVE: The purpose of this study was to analyze the correlation between the genetic constitution and the phenotype in triploid pregnancies. STUDY DESIGN: One hundred fifty-eight triploid pregnancies were identified in hospitals in Western Denmark from April 1986 to April 2010. Clinical data and karyotypes were collected retrospectively, and archived samples were retrieved. The parental origin of the genome, either double paternal contribution (PPM) or double maternal contribution (MMP) was determined by an analysis of methylation levels at imprinted sites. RESULTS: There were significantly more PPM than MMP cases (P < .01). In MMP cases, the possible karyotypes had similar frequencies, whereas, in PPM cases, 43% had the karyotype 69,XXX, 51% had the karyotype 69,XXY, and 6% had the karyotype 69,XYY. Molar phenotype was seen only in PPM cases. However, PPM cases with a nonmolar phenotype were also seen. For both parental genotypes, various fetal phenotypes were seen at autopsy. Levels of human chorionic gonadotropin in maternal serum were low in MMP cases and varying in PPM cases, some being as low as in the MMP cases. CONCLUSION: In a triploid pregnancy, suspicion of hydatidiform mole at ultrasound scanning, by macroscopic inspection of the evacuated tissue, at histology, or because of a high human chorionic gonadotropin in maternal serum level each predict the parental type PPM with a very high specificity. In contrast, the sensitivity of these observations was <100%.

Heart defects and other features of the 22q11 distal deletion syndrome.

22q11.2 distal deletion syndrome is distinct from the common 22q11.2 deletion syndrome and caused by microdeletions localized adjacent to the common 22q11 deletion at its telomeric end. Most distal deletions of 22q11 extend from LCR22-4 to an LCR in the range LCR22-5 to LCR22-8. We present three patients with 22q11 distal deletions, of whom two have complex congenital heart malformation, thus broadening the phenotypic spectrum. We compare cardiac malformations reported in 22q11 distal deletion to those reported in the common 22q11 deletion syndrome. We also review the literature for patients with 22q11 distal deletions, and discuss the possible roles of haploinsufficiency of the MAPK1 gene. We find the most frequent features in 22q11 distal deletion to be developmental delay or learning disability, short stature, microcephalus, premature birth with low birth weight, and congenital heart malformation ranging from minor anomalies to complex malformations. Behavioral problems are also seen in a substantial portion of patients. The following dysmorphic features are relatively common: smooth philtrum, abnormally structured ears, cleft palate/bifid uvula, micro-/retrognathia, upslanting palpebral fissures, thin upper lip, and ear tags. Very distal deletions including region LCR22-6 to LCR22-7 encompassing the SMARCB1-gene are associated with an increased risk of malignant rhabdoid tumors.

Small RNAs controlling outer membrane porins.

Gene regulation by small non-coding RNAs has been recognized as an important post-transcriptional regulatory mechanism for several years. In Gram-negative bacteria such as Escherichia coli and Salmonella, these RNAs control stress response and translation of outer membrane proteins and therefore are key regulators of environmental stress. Recent work has revealed an intimate interplay between small RNA regulation of outer membrane proteins and the stress-induced sigmaE-signalling system, which has an essential role in the maintenance of the integrity of the outer membrane.

TodK, a putative histidine protein kinase, regulates timing of fruiting body morphogenesis in Myxococcus xanthus.

In response to starvation, Myxococcus xanthus initiates a developmental program that results in the formation of spore-filled multicellular fruiting bodies. Fruiting body formation depends on the temporal and spatial coordination of aggregation and sporulation. These two processes are induced by the cell surface-associated C signal, with aggregation being induced after 6 h and sporulation being induced once cells have completed the aggregation process. We report the identification of TodK, a putative histidine protein kinase of two-component regulatory systems that is important for the correct timing of aggregation and sporulation. Loss of TodK function results in early aggregation and early, as well as increased levels of, sporulation. Transcription of todK decreases 10-fold in response to starvation independently of the stringent response. Loss of TodK function specifically results in increased expression of a subset of C-signal-dependent genes. Accelerated development in a todK mutant depends on the known components in the C-signal transduction pathway. TodK is not important for synthesis of the C signal. From these results we suggest that TodK is part of a signal transduction system which converges on the C-signal transduction pathway to negatively regulate aggregation, sporulation, and the expression of a subset of C-signal-dependent genes. TodK and the SdeK histidine protein kinase, which is part of a signal transduction system that converges on the C-signal transduction pathway to stimulate aggregation, sporulation, and C-signal-dependent gene expression, act in independent genetic pathways. We suggest that the signal transduction pathways defined by TodK and SdeK act in concert with the C-signal transduction pathway to control the timing of aggregation and sporulation.