While many genes perform their roles flawlessly, variations in others can lead to specific health conditions. The gene known as CC2D2A is one such example, playing a significant role in human health and development.
Cellular Function of CC2D2A
The CC2D2A gene provides instructions for creating a protein that is involved in the formation and function of tiny, hair-like structures found on the surface of nearly all human cells, called cilia. Cilia extend from the cell membrane and act like cellular antennae, coordinating various signaling pathways essential for development and physiological processes. They are also involved in fluid movement and sensing the extracellular environment.
The CC2D2A protein specifically localizes to the basal body and the transition zone of cilia. The basal body is the foundation from which cilia grow, and the transition zone acts as a gateway, controlling which proteins enter and exit the cilium. The CC2D2A protein is believed to be essential for the proper assembly of subdistal appendages, which are structures that anchor cytoplasmic microtubules and prepare the basal body for cilium formation.
Without properly functioning CC2D2A, cilia may not form correctly or may be entirely absent in certain tissues. This disruption in ciliary structure or function can lead to a group of genetic disorders known as ciliopathies. The protein also plays a part in the tectonic-like complex at the transition zone, which prevents the unwanted diffusion of proteins between the cilium and the main cell membrane. Furthermore, CC2D2A has been suggested to act as a sensor for intracellular calcium.
CC2D2A-Related Disorders
When the CC2D2A gene does not function as it should, it can lead to specific genetic disorders, primarily those categorized as ciliopathies. Two of the most common and significant disorders linked to CC2D2A mutations are Joubert Syndrome (JS) and Meckel-Gruber Syndrome (MKS).
Joubert Syndrome is a neurological disorder characterized by low muscle tone, problems with balance and coordination, and developmental delays. A distinguishing feature, often seen on brain imaging, is the “molar tooth sign,” which indicates a specific malformation of the brainstem and cerebellum. Additional symptoms can include unusual eye movements, breathing abnormalities, kidney and liver issues, extra fingers or toes, and vision loss. The severity and combination of these symptoms can vary widely among individuals.
Meckel-Gruber Syndrome represents a more severe form of CC2D2A-related ciliopathy, often leading to stillbirth or death shortly after birth. This condition is characterized by a triad of serious birth defects: brain malformations, typically an encephalocele (a sac-like protrusion of the brain), large polycystic kidneys, and polydactyly (extra fingers or toes). Other possible abnormalities include heart defects, cleft lip and palate, underdeveloped lungs, and liver fibrosis.
Genetic Inheritance and Detection
CC2D2A-related disorders follow an autosomal recessive inheritance pattern. This means that a child must inherit two altered copies of the CC2D2A gene, one from each parent, to develop the condition. Parents who carry one altered copy of the gene typically do not show symptoms themselves and are referred to as carriers.
For each child born to two carrier parents, there is a 25% chance of inheriting both altered genes and developing the condition. There is also a 50% chance the child will be an unaffected carrier, and a 25% chance they will inherit two unaffected genes.
Genetic testing is the primary method used to identify these genetic variations, which can confirm a diagnosis in affected individuals, identify carriers within a family, or be used for prenatal screening during pregnancy.