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Objective: The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition., Methods: A literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex., Results: We identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes., Conclusion: Multiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA., (© 2024 John Wiley & Sons Ltd.)

Sim2 is a member of the basic helix-loop-helix PAS transcription factor gene family and is evolutionarily related to the Drosophila single-minded gene, a key regulator of central nervous system midline development. In an effort to determine the biological roles of Sim2 in mammalian development, we disrupted the murine Sim2 gene through gene targeting. Mice homozygous for the disrupted allele (Sim2 -/-) exhibit a cleft of the secondary palate and malformations of the tongue and pterygoid processes of the sphenoid bone. These craniofacial malformations are the most probable cause of aerophagia (air swallowing with subsequent accumulation of air in the gastrointestinal tract) and postnatal death exhibited by Sim2 -/- mice. The developing palates of the Sim2 -/- mice are hypocellular, and at embryonic day 14.5 contain excess extracellular matrix component hyaluronan (HA) compared with heterozygotes and homozygous wild-type littermates. HA plays an important role in the regulation and mechanics of palate development. Its premature accumulation in Sim2 -/- animal palates suggests a regulatory role for Sim2 in HA synthesis and in the establishment of craniofacial architecture., (Copyright 2002 Wiley-Liss, Inc.)

The formation of cardiac cushion tissue, which ultimately contributes to formation of the valves and septa, is dependent on the regional activation of cardiac endothelial cells to undergo an epithelial-mesenchymal transition. This endothelial transition was correlated with activin betaA mRNA expression by Northern and in situ hybridization in both a temporal and spatial manner in developing mouse embryos. Activin betaA was the only subunit of the inhibin family detected during the initial phase of endothelial cell transition; activin betaB was detected at later stages, and inhibin alpha was not detectable in the heart. An in vitro assay that has been used to study mesenchymal cell formation in chick was modified for use with mammalian embryos. Conditioned media from embryonic mouse cardiocyte cultures was shown to substitute for the endogenous inductive signal in these assays. The presence of activin betaA was demonstrated by Western blot analysis of the cardiocyte conditioned media (CCM). Modified antisense oligonucleotides to activin betaA inhibited the endothelial-mesenchymal transition in the assay system, which was not affected by control oligonucleotides. Adapting the avian culture system for use with mice enabled the use of tissue from mice with a null allele for activin betaA. CCM produced from embryos homozygous for the mutant betaA allele did not contain activin betaA and was used in in vitro assays. CCM lacking activin betaA produced fewer mesenchymal cells from cardiac endothelial monolayers than CCM with activin betaA. Localized expression of activin betaA in the embryonic heart indicates a possible role in the endothelial-mesenchymal transition. Bioassays in which activin betaA expression is blocked or activin betaA is absent from the media indicate that activin betaA promotes the formation of mesenchymal cells in the endothelial cushions, which are required for normal septation.

Using nuclear morphometric analysis, a retrospective study was made of 27 patients with Wilms' tumor. The blinded group consisted of 17 patients with Stage I and II favorable-histology Wilms' tumors who did not respond to therapy and ten patients with Stage III and IV favorable-histology Wilms' tumors who did respond. In this complex group of patients, multivariate analysis (with several morphologic descriptors) was used to predict which patients responded to therapy. No single-shape descriptor predicted the response to therapy (P greater than 0.5). However, three shape descriptors: maximum ellipticity (ME), standard error of bending energy (SEBE), and the range of chain code-maximum peak (RCCM), with the multivariate formula of (1131 x SEBE) + (-7 x ME) + (50 x RCCM) + 7.18, separated the two groups (P less than 0.004). This result was statistically significant. Using this multivariate equation and a cutoff value of 0.6 units, this test yielded a sensitivity of 94% and a specificity of 70%. This result, in a complex group of patients, suggests that nuclear morphometry may be useful in the initial assessment of patients with Wilms' tumor and warrants further analysis.