AI Article Synopsis
- A study examined a group of fetuses in France diagnosed with localized overgrowth disorders (LOD) suspected to be linked to genetic changes in the PI3K-AKT-mTOR signaling pathway.
- Researchers reviewed data from 2013 to 2020, focusing on fetuses with brain and limb overgrowth, analyzing tissue from autopsies and amniotic fluid for genetic variants.
- Out of 21 cases, several specific genetic variants were found, particularly in fetuses with isolated megalencephaly and hemimegalencephaly, indicating a significant connection between these overgrowth conditions and certain genetic abnormalities.
Article Abstract
Objectives: To describe clinical and molecular findings in a French multicenter cohort of fetuses with prenatal diagnosis of congenital abnormality and suspicion of a localized overgrowth disorder (LOD) suggestive of genetic variants in the PI3K-AKT-mTOR signaling pathway.
Methods: We analyzed retrospectively data obtained between 1 January 2013 and 1 May 2020 from fetuses with brain and/or limb overgrowth referred for molecular diagnosis of PI3K-AKT-mTOR pathway genes by next-generation sequencing (NGS) using pathological tissue obtained by fetal autopsy. We also assessed the diagnostic yield of amniotic fluid.
Results: During the study period, 21 subjects with LOD suspected of being secondary to a genetic variant of the PI3K-AKT-mTOR pathway were referred for analysis. Of these, 17 fetuses had brain overgrowth, including six with isolated megalencephaly (MEG) and 11 with hemimegalencephaly (HMEG). Of the six with MEG, germline variants were identified in four cases, in either PIK3R2, AKT3 or MTOR, and a postzygotic PIK3R2 variant was found in the other two cases. Of the 11 with HMEG, a postzygotic PIK3CA variant was found in three fetuses with extracerebral features of PIK3CA-related overgrowth spectrum, and in seven fetuses with isolated HMEG. No pathogenic variant was identified in the 11 case with HMEG. Four fetuses with limb overgrowth also had one or more lymphatic malformations (LM) and harbored a postzygotic PIK3CA variant. NGS on cultured amniocytes performed in 10 cases, of which nine had been found positive on analysis of pathological fetal tissue, showed variants in four, in either PIK3CA, PIK3R2 or AKT3.
Conclusions: Isolated MEG or HMEG may lead to identification of genetic variants in the PI3K-AKT-mTOR signaling pathway. Cases of limb overgrowth and LM or isolated HMEG are likely associated with PIK3CA variants. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/uog.23715 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The role of genetic sequencing in the diagnostic work-up for chronic immune thrombocytopenia.
Blood Adv
January 2025
Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom, London, United Kingdom.
Immune Thrombocytopenia (ITP) is a heterogenous autoimmune disorder diagnosed by excluding other conditions. Misdiagnosis of primary ITP occurs in patients with inherited thrombocytopenia and primary immunodeficiency syndromes. This study investigates whether genetic testing for inherited thrombocytopenia or primary immunodeficiency can enhance diagnostic accuracy in ITP, and guide treatment strategies.
View Article and Find Full Text PDFDiscovery of non-retinoid compounds that suppress the pathogenic effects of misfolded rhodopsin in a mouse model of retinitis pigmentosa.
PLoS Biol
January 2025
Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
Pathogenic mutations that cause rhodopsin misfolding lead to a spectrum of currently untreatable blinding diseases collectively termed retinitis pigmentosa. Small molecules to correct rhodopsin misfolding are therefore urgently needed. In this study, we utilized virtual screening to search for drug-like molecules that bind to the orthosteric site of rod opsin and improve its folding and trafficking.
View Article and Find Full Text PDFPKCδ germline variants and genetic deletion in mice augment antitumor immunity through regulation of myeloid cells.
Cancer Immunol Res
January 2025
University of Chicago, Chicago, IL, United States.
Based on the notion that hypomorphic germline genetic variants are linked to autoimmune diseases, we reasoned that novel targets for cancer immunotherapy might be identified through germline variants associated with greater T-cell infiltration into tumors. Here, we report that while investigating germline polymorphisms associated with a tumor immune gene signature, we identified PKCδ as a candidate. Genetic deletion of PKCδ in mice resulted in improved endogenous antitumor immunity and increased efficacy of anti-PD-L1.
View Article and Find Full Text PDFA novel COL3A1 gene variant associated with sudden death due to spontaneous pneumothorax.
Forensic Sci Med Pathol
January 2025
Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Spontaneous pneumothorax (SP) is a condition defined by abnormal gas accumulation in the chest cavity. Mutations of the collagen type III alpha 1 chain, COL3A1 gene, are primarily linked to vascular Ehlers-Danlos syndrome (vEDS); however, they can also contribute to structural changes in the tissue, like bullae of the lungs. In this case report, we present a young, thinly built boy who died due to a spontaneous pneumothorax.
View Article and Find Full Text PDFHawks, Doves, and Perissodus microlepis. Undermining the selected effects theory of function.
Hist Philos Life Sci
January 2025
Department Civilization and Forms of Knowledge, University of Pisa, Pisa, PI, Italy.
The selected effects theory is supposed to provide a fully naturalistic basis for statements about what biological traits or processes are for without appeal to final causes or intelligent design. On the selected effects theory, biologists are allowed to say, for instance, that hindwing eyespots on butterfly wings serve to deflect predators' attacks away from vital organs because a similar fitness-enhancing effect explains why eyespots themselves were favoured by natural selection and persisted in the population. This is known as the explanatory dimension of the selected effects theory.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!