DCTN1

MedlinePlus Genetics provides information about Amyotrophic lateral sclerosis

At least five mutations in the DCTN1 gene have been found to cause Perry syndrome. This progressive brain disease is characterized by a pattern of movement abnormalities known as parkinsonism, psychiatric changes, weight loss, and abnormally slow breathing (hypoventilation).

Most of the mutations that cause Perry syndrome change single protein building blocks (amino acids) in the dynactin-1 protein. These genetic changes impair the ability of the p150-glued version of dynactin-1 to bind to the dynactin complex and to microtubules. An incomplete dynactin complex has a reduced ability to transport materials within cells. Slow or abnormal transport of materials needed for the normal function of neurons causes these cells to malfunction and ultimately die. A gradual loss of neurons in areas of the brain that regulate movement, emotion, and breathing underlies the signs and symptoms of Perry syndrome.

MedlinePlus Genetics provides information about Charcot-Marie-Tooth disease

Researchers have identified at least one DCTN1 gene mutation that causes a nervous system disorder called distal hereditary motor neuronopathy type VIIB. Signs and symptoms of this disorder first appear in early adulthood and include breathing difficulties and progressive weakness of muscles in the face and hands. Muscle weakness in the feet and legs develops later. The mutation that causes this disorder changes one of the amino acids used to make dynactin-1. Specifically, it replaces the amino acid glycine with the amino acid serine at protein position 59 (written as Gly59Ser or G59S). It is unclear how this mutation causes distal hereditary motor neuronopathy type VIIB. The altered protein may result in an abnormal dynactin complex and disturb interactions between the complex and microtubules, which would disrupt transport activities and impair the function of axons in neurons.

At least one DCTN1 gene mutation is associated with a brain disorder called frontotemporal dementia (FTD) without the features of amyotrophic lateral sclerosis (ALS). This disorder occurs in mid- to late adulthood and is characterized by changes in personality and behavior that may make it difficult for affected individuals to interact with others in a socially appropriate manner. Changes in speech and language can also occur, such as problems using the correct word and difficulty with language comprehension. The DCTN1 gene mutation associated with this disorder replaces the amino acid arginine with the amino acid lysine at protein position 1101 (written as Arg1101Lys or R1101K). It is unclear how this mutation causes FTD. This mutation likely alters the 3-dimensional shape of dynactin-1, which may impair its binding with the dynactin complex and microtubules. This impaired binding may slow the transport of materials needed for the proper function of axons and the efficient transmission of nerve impulses.