FLNA gene

The FLNA gene provides instructions for producing filamin A, a protein that helps maintain the cell's internal structure and regulates various developmental processes.

Normal Function

The FLNA gene provides instructions for producing the protein filamin A, which helps build the cell's internal network of protein filaments called the cytoskeleton. The cytoskeleton gives structure to cells and allows them the flexibility to change shape. Filamin A primarily attaches (binds) to actin to form the branching network of filaments that make up the cytoskeleton.

Filamin A also binds to many other proteins to carry out functions including cell adhesion, cell migration, determination of cell shape, and cell survival. These functions play roles in regulating skeletal and brain development, heart tissue and blood vessel formation, blood clotting, skin elasticity, lung tissue maintenance, and digestive system function.

Health Conditions Related to Genetic Changes

Otopalatodigital spectrum disorders

Variants in the FLNA gene are associated with a group of related conditions known as otopalatodigital spectrum disorders. These include:

• Frontometaphyseal dysplasia: Involves skeletal development abnormalities, particularly in the joints, and kidney, heart, and airway defects.
• Melnick-Needles syndrome: Typically the most severe of these disorders, involving short stature, abnormal spine curvature, and partial joint dislocation.
• Otopalatodigital syndrome type 1: Typically the mildest, characterized by hearing loss, cleft palate, and skeletal abnormalities in the digits.
• Otopalatodigital syndrome type 2: Similar to type 1 but with more severe skeletal development abnormalities.
• Terminal osseous dysplasia: Characterized by skeletal abnormalities in the hands and feet, benign tumors on the digits, and dark skin patches on the face.

Most of these variants are "gain of function," enhancing the activity of filamin A or giving it a new function, which disrupts skeletal development.

Periventricular heterotopia

Hundreds of FLNA gene variants have been identified in individuals with periventricular heterotopia. Most of these variants result in a lack of filamin A protein, causing a disorganized cytoskeleton and impaired cell adhesion. This prevents neurons from migrating properly during fetal brain development, leading to clumps of neurons (nodules) around the brain's ventricles, which causes seizures and other neurological problems.

Intestinal pseudo-obstruction

Variants in the FLNA gene can cause intestinal pseudo-obstruction, characterized by impaired muscle contractions in the digestive tract. These are often "loss of function" variants that reduce filamin A levels, causing abnormal layering of smooth muscles in the gastrointestinal tract.

X-linked cardiac valvular dysplasia

Variants in the FLNA gene can cause X-linked cardiac valvular dysplasia, characterized by abnormally thick heart valves. These variants alter the protein's shape, impairing its ability to bind to actin and weakening the cell cytoskeleton, which prevents heart valves from opening and closing normally.

Genomic Location

The FLNA gene is found on the X chromosome.