Hyaline fibromatosis syndrome (HFS) - ANTXR2 gene
Hyaline fibromatosis syndrome (HFS), also known as Murray-Puretic syndrome, is a variable severity process in which hyaline accumulates abnormally in body tissues. This process affects many areas of the body, including skin, joints, bones and internal organs.
Signs and symptoms related to this process include the development of nodules under the skin, which can cause pain and complications, such as the development of protein loss enteropathy as a result of the formation of nodules in the intestines. Often painful nodules appear on the hands, neck, scalp, ears and nose. Other signs associated with this disease are hyperpigmentation and thickening of the skin; gingival hypertrophy; joint stiffness and pain; and development of contractures and bone abnormalities.
In the most severe cases (infantile systemic hyalinosis –ISH-) the signs and symptoms appear at birth, or they begin in the first months of life, and can be fatal. In milder cases (juvenile hyaline fibromatosis –JHF-) the signs and symptoms begin in childhood and affect fewer body systems.
This process is due to mutations in the ANTXR2 gene (ANTXR cell adhesion molecule 2), located on the long arm of chromosome 4 (4q21.21), which encodes a protein that is found on the surface of many cell types. It is believed that the ANTXR2 protein interacts with the components of the extracellular matrix. This protein is involved in the formation of capillaries and in the maintenance of the structure of the basement membranes. It is believed that the ANTXR2 protein aids in the breakdown of at least one type of extracellular matrix protein, ensuring that the correct balance of proteins is maintained for normal functioning of the muscles and connective tissues. In addition, the ANTXR2 protein also acts as a receptor for the toxin that causes anthrax, which allows the toxin to adhere to the cells and trigger the disease.
More than 45 mutations in the ANTXR2 gene have been described in individuals with hyaline fibromatosis syndrome. Some identified mutations reduce or eliminate the amount of ANTXR2 protein on the surface of cells. It is believed that other mutations affect the ability of the protein to interact with the components of the extracellular matrix. Although it is not clear what effect these mutations have on cells and tissues, it is believed that genetic mutations interrupt the formation of basal membranes, allowing hyaline to seep and accumulate in various body tissues. Alternatively, the mutations could alter the breakdown of excess extracellular matrix proteins, which then accumulate in the tissues and give rise to the signs and symptoms of hyaline fibromatosis syndrome.
This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with hyaline fibromatosis syndrome (HFS), by means of the complete PCR amplification of the exons of the ANTXR2 gene, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).