FKTN

Several different variants (also called mutations) in the FKTN gene have been found to cause Fukuyama congenital muscular dystrophy, a condition that affects the development of the eyes, brain, and skeletal muscles. This form of congenital muscular dystrophy occurs primarily in people of Japanese ancestry. 

Most people with Fukuyama congenital muscular dystrophy have at least one copy of a particular variant: an insertion of about 3,000 extra DNA building blocks (nucleotides) in the FKTN gene. This DNA insertion occurs in a part of the FKTN gene that regulates the gene's activity. Researchers believe that this DNA insertion reduces the amount of functional fukutin that is produced from the gene.

A shortage of fukutin impacts the normal glycosylation of alpha-dystroglycan. As a result, alpha-dystroglycan can no longer effectively anchor cells to the extracellular matrix. Without enough functional alpha-dystroglycan to stabilize the muscle fibers, the fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, which affects the development, structure, and function of skeletal muscles in people with Fukuyama congenital muscular dystrophy.

A decrease in the amount of functional alpha-dystroglycan also affects the migration of neurons during the early development of the brain. This causes a brain abnormality called cobblestone lissencephaly, in which the surface of the brain appears bumpy and irregular and lacks the normal folds and grooves. Less is known about the effects of FKTN gene variants in other parts of the body.

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Variants in the FKTN gene can also cause Walker-Warburg syndrome, a severe form of congenital muscular dystrophy that affects the development of the eyes, brain, and skeletal muscles. The eye and brain abnormalities seen in those with Walker-Warburg syndrome are often more severe than those seen in people with Fukuyama congenital muscular dystrophy. Children with Walker-Warburg syndrome tend to survive only into infancy or early childhood. The FKTN gene variants associated with this condition prevent the production of functional fukutin protein, which leads to the severe muscle, eye, and brain problems that are characteristic of Walker-Warburg syndrome.

Variants in the FKTN gene have also been associated with another congenital muscular dystrophy called muscular dystrophy-dystroglycanopathy, type B4 (MDDGB4). People with MDDGB4 typically have muscle weakness and delayed development of motor skills.