Baraitser-Winter syndrome ... (Baraitser-Winter syndrome) - Genes ACTB and ACTG1.
The Baraitser-Winter syndrome is a disorder that affects the development of many parts of the body, especially the face and brain.
The most common feature of the syndrome is unusual facial appearance, which may include hypertelorism, droopy eyelids with large openings, very arched eyebrows, a nose bridge and tip wide nose, philtrum, prominent cheeks and pointy chin. In most people there are also structural brain abnormalities associated with abnormal neuronal migration, not occupying the places that should. The most common brain abnormality is pachygyria, which corresponds to a brain area with an abnormally smooth surface with fewer convolutions. Less frequently, affected individuals have lissencephaly, ie all smooth brain surface. These structural changes can cause mild to profound intellectual disability, developmental delay and seizures.
Other features of the syndrome may include short stature, ear anomalies and hearing loss, heart defects, the presence of an extra thumb, and abnormalities of the kidneys and urinary system. Some affected individuals have limited mobility of large joints such as elbows and knees, which can be present at birth or develop over time. Rarely, people with dystonia syndrome have.
This process is due to mutations in the ACTB gene, located on the short arm of chromosome 7 (7p22) or mutations in the ACTG1 gene, located on the long arm of chromosome 17 (17q25). These genes encode the proteinase beta (?) and gamma-actin (?) actin, respectively. These proteins are active in cells throughout the body, which are organized into a network of fibers called the actin cytoskeleton, which constitutes the structural framework of the cell. The actin cytoskeleton has several critical functions, including the determination of cell shape and allowing the cells to move.
Mutations in the gene ACTB ACTG1 or alter the function of the ?-actin or ?-actin. A malfunctioning actin causes changes in the actin cytoskeleton modifying the structure and organization of cells and affects their ability to move. Because these two proteins are present in cells throughout the body and participate in many cell activities, problems with its function likely impact on many aspects of development, including neuronal migration. These changes underlie the variety of signs and symptoms associated with the syndrome.
Mutations in the gene ACTB, change the amino acids of the ?-actin. The most common mutation replaced arginine by histidine at position 196 of the protein (or Arg196His R196H).
They have identified at least six mutations in the gene that cause ACTG1 syndrome. Known mutations change the amino acids in the ?-actin. The most common mutation replaces the amino acid serine to phenylalanine amino acid at position 155 of protein (Ser155Phe or S155F).
Baraitser syndrome-Winter has a pattern of autosomal dominant, which means a copy of the altered gene in each cell is sufficient to cause the disorder.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Baraitser-Winter, by complete PCR amplification of the exons of ACTB and ACTG1 genes, respectively, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).