Roberts syndrome/SC phocomelia (RBS) is an autosomal recessive disorder with growth retardation, craniofacial abnormalities and limb reduction. Cellular alterations in RBS include lack of cohesion at the heterochromatic regions around centromeres and the long arm of the Y chromosome, reduced growth capacity, and hypersensitivity to DNA damaging agents. RBS is caused by mutations in ESCO2, which encodes a protein belonging to the highly conserved Eco1/Ctf7 family of acetyltransferases that is involved in regulating sister chromatid cohesion. We identified 10 new mutations expanding the number to 26 known ESCO2 mutations. We observed that these mutations result in complete or partial loss of the acetyltransferase domain except for the only missense mutation that occurs in this domain (c.1615T>G, W539G). To investigate the mechanism underlying RBS, we analyzed ESCO2 mutations for their effect on enzymatic activity and cellular phenotype. We found that ESCO2 W539G results in loss of autoacetyltransferase activity. The cellular phenotype produced by this mutation causes cohesion defects, proliferation capacity reduction and mitomycin C sensitivity equivalent to those produced by frameshift and nonsense mutations associated with decreased levels of mRNA and absence of protein. We found decreased proliferation capacity in RBS cell lines associated with cell death, but not with increased cell cycle duration, which could be a factor in the development of phocomelia and cleft palate in RBS. In summary, we provide the first evidence that loss of acetyltransferase activity contributes to the pathogenesis of RBS, underscoring the essential role of the enzymatic activity of the Eco1p family of proteins.

Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins (Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer’s disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.

Objective: This systematic review analyzes the anatomical variants in the pancreas and its ductal system to report on their association with pancreatic pathologies. Methods: We conducted a search of the MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception to July 2023. The methodological quality was assessed with the Anatomical Quality Assessment (AQUA) tool. Finally, the pooled prevalence was estimated using a random effects model. Results: 55 studies were found that met the eligibility criteria. The overall prevalence of pancreas divisum (PD) was 18% (95% CI = 15–21%). The prevalence of PD associated with pancreatitis was 30% (95% CI = 1–61%). Conclusions: An anatomical variant of the pancreas such as PD may be the cause of bile duct obstruction, resulting in various clinical complications, such as pancreatitis. Hence, knowing this variant is extremely important for surgeons, especially for those who treat the gastroduodenal region.

Background: The internal jugular vein (IJV) is a vascular structure that is responsible for the venous drainage of both the head and neck and is commonly found posterior to the internal carotid artery and adjacent to cervical lymph nodes or nerve structures such as the glossopharyngeal and accessory nerves. As a vagal nerve, it is an important reference point for surgical access in neck interventions and dissections. Methods: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were searched until August 2024. Methodological quality was evaluated with an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. Results: A total of 10 studies met the established selection criteria in this meta-analysis study. The prevalence of variants of the IJV was 3.36% (CI: 2.81–6.96%), with a heterogeneity of 94.46%. Regarding the subgroup analysis, no study presents statistically significant differences in the studies analyzed for this review. Conclusions: Knowing the IJV variants in detail will make early diagnosis useful, especially in surgeries in the neck region and in classic surgeries such as thyroidectomies and tracheostomies, among others. It will be important to know the position of the IJV.

Disecando la crisis de la anatomía

Introducción: el asesoramiento genético es una práctica que puede enmarcarse en cuatro escenarios: preconcepcional, preimplantación, prenatal y posnatal (similar al preconcepcional). Para algunos autores este tipo de práctica se considera eugenesia. El objetivo del presente artículo es exponer los distintos puntos de vista, descritos en la literatura, sobre la relación del asesoramiento genético con la eugenesia. Materiales y métodos: se buscaron artículos en bases de datos académicas con los términos MeSH/DeCS bioética, genética médica, asesoramiento genético y eugenesia. Se incluyeron artículos que hablaran sobre eugenesia o sobre cribaje genético; se excluyeron artículos con la descripción técnica de procedimientos. La selección se realizó por título, resumen y texto completo. Resultados: se seleccio- naron 57 artículos para el análisis. En el asesoramiento preconcepcional, el “principio de bene cencia procreativa” se considera que parte de posturas similares a las prácticas eugenésicas de principios del siglo xx. En la consulta preimplantación, la selección genética de embriones puede considerarse eugenesia cuando se usa para alterar el curso natural de la procreación o para nes no médicos. El diagnóstico prenatal, cuando se vincula con el aborto por malformaciones congénitas, puede conside- rarse eugenesia negativa. Discusión: en la actualidad, la eugenesia abarca múltiples de niciones. Según la de nición escogida, el asesoramiento genético puede enmarcarse como una práctica eugenésica. Sin embargo, el diseño de políticas de salud y el interés de la sociedad puede in uir en la autonomía de los individuos. Por otro lado, la posibilidad de generar una selección genética de individuos puede constituirse como eugenesia positiva.