Fibrillin2

Fibrillin-2 (FBN2) is a large secreted extracellular matrix glycoprotein that is a major component of microfibrils in connective tissues. It is encoded by the FBN2 gene in humans. Fibrillin-2 monomers assemble into microfibrils that provide structural support and contribute to the deposition of elastin in developing tissues. The protein contains multiple calcium-binding epidermal growth factor-like repeats and transforming growth factor beta–binding protein-like domains, enabling its assembly into filamentous networks and interaction with other extracellular matrix components.

Distribution and function: Fibrillin-2 is expressed in fetal tissues and is particularly important during skeletal development, limb formation, and organogenesis. In adults, it contributes to the structural integrity of elastic fibers in skin, lungs, and blood vessels and participates in the regulation of TGF-β signaling by binding latent TGF-β complexes, influencing signaling pathways that control matrix remodeling.

Genetic diseases: Mutations in FBN2 cause congenital contractural arachnodactyly (Beals syndrome), an autosomal dominant connective tissue disorder characterized by arachnodactyly, contractures of large joints, scoliosis, and crumpled ears. Mutations are typically located in regions encoding calcium-binding EGF-like and TB domains and can disrupt microfibril assembly, leading to connective tissue defects. FBN2 mutations are genetically distinct from FBN1-related Marfan syndrome, though both affect microfibrillar architecture and signaling pathways.

Genetics and research: The FBN2 gene is located on chromosome 6q23-q24. Animal models, including Fbn2-deficient mice, help elucidate the role of fibrillin-2 in development and microfibril formation. Understanding FBN2 function aids diagnosis via genetic testing and informs potential approaches targeting TGF-β signaling in related conditions.