Related Experiment Video
Updated: Sep 18, 2025
07:07
Evaluation of Planar-Cell-Polarity Phenotypes in Ciliopathy Mouse Mutant Cochlea
Published on: February 21, 2016
10.6K
PIK3C2A-Related Clinical Phenotype and Cellular Charaterization Linked to Functional SHH Primary Cilia Defect
Adella Karam1, Clarisse Delvallée1, Bénédicte Gérard2
1Laboratoire de Génétique médicale, UMR_S INSERM U1112, Institut de Génétique Médicale D'alsace (IGMA), Université de Strasbourg, Strasbourg, France.
Clinical Genetics
|June 21, 2025
Summary
PIK3C2A gene variants cause a rare syndrome affecting development. This study identifies new variants linked to cataracts and deafness, expanding the known PIK3C2A-related disorder spectrum.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Phosphatidylinositol-3-kinases (PI3K) are crucial for cell signaling.
- PIK3C2A, a class II PI3K, regulates cell growth, motility, and cilia function.
- PIK3C2A variants are linked to oculoskeletodental syndrome (OCSKD).
Purpose of the Study:
- To investigate the PIK3C2A gene in a family with a novel PIK3C2A-related syndrome.
- To characterize the clinical and molecular features of this new presentation.
- To understand the functional consequences of identified PIK3C2A variants.
Main Methods:
- Trio exome sequencing to identify genetic variants.
- Functional testing of patient-derived skin fibroblasts.
- Analysis of protein levels, enzyme activity, and cellular phenotypes (cilia, proliferation).
Main Results:
- Two novel compound heterozygous PIK3C2A variants were identified.
- Patient fibroblasts showed normal PIK3C2A protein levels but defective enzyme activity.
- Impaired cilia formation/function and reduced proliferative capacity were observed in patient cells.
Conclusions:
- This study expands the clinical and mutational spectrum of PIK3C2A-related disorders.
- The findings highlight the role of PIK3C2A in ocular and auditory development.
- Functional studies are essential for understanding the pathogenicity of PIK3C2A variants.
Related Concept Videos
01:22Microtubules in Signaling
1.8K
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
1.8K
02:33Hedgehog Signaling Pathway
7.5K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.5K
01:09Cytoskeletal Linker Proteins - Plakins
2.4K
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.4K
01:33Pleiotropy
41.2K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
41.2K
03:14Notch Signaling Pathway
4.5K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.5K