FLNA

The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape and move. Filamin A binds to another protein called actin and helps it form the branching network of filaments that make up the cytoskeleton. Filamin A also links actin to many other proteins to perform various functions within the cell, including regulating skeletal and brain development, the formation of blood vessels, and blood clotting.

frontometaphyseal dysplasia - caused by mutations in the FLNA gene

A small number of mutations in regions of the FLNA gene called exons 4, 22, 29, 33, and 44 through 46 have been identified in people with frontometaphyseal dysplasia. These mutations are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Different mutations appear to produce specific changes in the protein, resulting in particular signs and symptoms that are classified as individual FLNA-related disorders. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of frontometaphyseal dysplasia.

intestinal pseudo-obstruction - caused by mutations in the FLNA gene

Intestinal pseudo-obstruction, a condition characterized by impairment of the muscle contractions that move food through the digestive tract (peristalsis), can be caused by mutations in the FLNA gene.

Some individuals with intestinal pseudo-obstruction have FLNA gene mutations that result in an abnormally short filamin A protein. Others have duplications or deletions of genetic material in the FLNA gene. Researchers believe that these genetic changes may impair the function of the filamin A protein, causing abnormalities in the cytoskeleton of nerve cells (neurons) in the gastrointestinal tract. These abnormalities result in impaired peristalsis, which causes abdominal pain and the other gastrointestinal symptoms of intestinal pseudo-obstruction.

Deletions or duplications of genetic material that affect the FLNA gene can also include adjacent genes on the X chromosome. Changes in adjacent genes may account for some of the other signs and symptoms, such as neurological abnormalities and unusual facial features, that occur in some affected individuals.

Melnick-Needles syndrome - caused by mutations in the FLNA gene

A small number of mutations in a region of the FLNA gene called exon 22 have been identified in people with Melnick-Needles syndrome. These mutations are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Different mutations appear to produce specific changes in the protein, resulting in particular signs and symptoms that are classified as individual FLNA-related disorders. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of Melnick-Needles syndrome.

otopalatodigital syndrome type 1 - caused by mutations in the FLNA gene

A small number of mutations in regions of the FLNA gene called exons 3, 4, and 5 have been identified in people with otopalatodigital syndrome type 1. The mutations all result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 1 are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Different mutations appear to produce specific changes in the protein, resulting in particular signs and symptoms that are classified as individual FLNA-related disorders. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 1.

otopalatodigital syndrome type 2 - caused by mutations in the FLNA gene

A small number of mutations in regions of the FLNA gene called exons 3, 4, and 5 have been identified in people with otopalatodigital syndrome type 2. Similar but more severe symptoms have been associated with mutations in exons 11 and 29. The mutations in exons 3, 4, and 5 result in changes to the filamin A protein in the region that binds to actin. The mutations responsible for otopalatodigital syndrome type 2 are described as "gain-of-function" because they appear to enhance the activity of the filamin A protein or give the protein a new, atypical function. Different mutations appear to produce specific changes in the protein, resulting in particular signs and symptoms that are classified as individual FLNA-related disorders. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of otopalatodigital syndrome type 2.

periventricular heterotopia - caused by mutations in the FLNA gene

More than 25 FLNA gene mutations have been identified in individuals with periventricular heterotopia. Most of these mutations result in a protein that is too short and cannot perform its function, resulting in the disruption of the cytoskeleton and impairment in cellular mobility. Nerve cells (neurons) that do not migrate properly during development form clumps around fluid-filled cavities (ventricles) near the center of the brain, resulting in the signs and symptoms of periventricular heterotopia.

In some cases, mutations result in the substitution of one protein building block (amino acid) for another amino acid in the protein sequence. These mutations may result in the production of a partially functional protein, causing a milder form of the disorder.