FTL

The FTL gene provides instructions for making the ferritin light chain, which is one part (subunit) of a protein called ferritin. Ferritin is made up of 24 subunits formed into a hollow spherical molecule. The 24 subunits consist of varying numbers of the ferritin light chain and another subunit called the ferritin heavy chain, produced from the FTH1 gene. The proportion of the two subunits varies in different tissues.

Ferritin stores and releases iron in cells. Each ferritin molecule can hold as many as 4,500 iron atoms inside its spherical structure. This storage capacity allows ferritin to regulate the amount of iron in cells and tissues.

neuroferritinopathy - caused by mutations in the FTL gene

At least four mutations in the FTL gene have been identified in people with neuroferritinopathy. These mutations all affect an area of the gene known as exon 4. The most common mutation detected in people with this disorder inserts the DNA building block (nucleotide) adenine between positions 460 and 461 in the gene sequence. Researchers believe that most families with this mutation descend from a common ancestor who lived in northwest England before 1800. Three other known mutations are each found in a single individual or family affected by neuroferritinopathy.

Mutations in the FTL gene that cause neuroferritinopathy are believed to reduce ferritin's ability to store iron, resulting in the release of excess iron in nerve cells (neurons) of the brain. The cells may respond by producing more ferritin in an attempt to handle the free iron. Excess iron and ferritin accumulate in the brain, particularly in certain regions that help to control movement (basal ganglia), resulting in the movement problems and other neurological changes seen in neuroferritinopathy.

other disorders - caused by mutations in the FTL gene

A disorder called hyperferritinemia-cataract syndrome is also caused by mutations in the FTL gene. Mutations that cause this disorder are found in a segment of the gene called the iron responsive element (IRE), in a larger area called the 5-prime noncoding region.

Individuals affected by this disorder have an excess of ferritin in the blood (hyperferritinemia) and clouding of the lens of the eyes (cataracts). Mutations in the IRE interfere with binding to a protein called the iron regulatory protein (IRP), which helps control the activity (expression) of the FTL gene. Impaired IRP binding disrupts the regulation of ferritin production, resulting in excess ferritin in the body. Accumulation of ferritin in the lens of the eyes is believed to cause the cataracts seen in this disorder.