ACTG1

The ACTG1 gene provides instructions for making a protein called gamma (γ)-actin, which is part of the actin protein family. Proteins in this family are organized into a network of fibers called the actin cytoskeleton, which makes up the structural framework inside cells. There are six types of actin; four are present only in muscle cells, where they are involved in the tensing of muscle fibers (muscle contraction). The other two actin proteins, γ-actin and beta (β)-actin (produced from the ACTB gene), are found in cells throughout the body. These proteins play important roles in determining cell shape and controlling cell movement (motility).

γ-actin is particularly abundant in certain cells in the intestines and the inner ear. Within the inner ear, this protein is found in specialized cells called hair cells, which are essential for normal hearing.

Baraitser-Winter syndrome - caused by mutations in the ACTG1 gene

At least six mutations in the ACTG1 gene have been found to cause Baraitser-Winter syndrome, a rare condition that affects the development of the brain, eyes, and other facial features. The known mutations change single protein building blocks (amino acids) in γ-actin. The most common mutation replaces the amino acid serine with the amino acid phenylalanine at protein position 155 (written as Ser155Phe or S155F). The mutations that cause Baraitser-Winter syndrome alter the function of γ-actin, which causes changes in the actin cytoskeleton that modify the structure and organization of cells and affect their ability to move. Because γ-actin is present in cells throughout the body and is involved in many cell activities, problems with its function likely impact many aspects of development. These changes underlie the variety of signs and symptoms associated with Baraitser-Winter syndrome.

nonsyndromic deafness - caused by mutations in the ACTG1 gene

Researchers have identified at least 10 ACTG1 gene mutations that cause a form of nonsyndromic deafness called DFNA20/26. "Nonsyndromic" means the hearing loss is not associated with signs and symptoms affecting other parts of the body.

The ACTG1 gene mutations that cause nonsyndromic hearing loss change single amino acids in γ-actin, which most likely alters the 3-dimensional shape of the protein. The altered protein probably causes hearing loss by impairing the function or survival of hair cells in the inner ear.

It is unclear why some ACTG1 gene mutations result in nonsyndromic hearing loss while others cause the more severe features of Baraitser-Winter syndrome.