Skeletal dysplasia related CHST3 (CHST3 skeletal dysplasia -related) - Gen CHST3.
Skeletal dysplasia CHST3 related gene is a genetic disease characterized by bone and joint abnormalities that worsen over time. Signs and symptoms associated with the disease may include short stature, congenital joint dislocations that most often affect the knees, hips and elbows, clubfoot, limited movements of large joints and abnormal curvature of the spine. The characteristics of skeletal dysplasia related gene CHST3 are generally limited to bones and joints. However, there have been minor heart defects in some affected individuals.
Sometimes this disease has been described as autosomal recessive syndrome Larsen its similarity to Larsen syndrome. Other nomenclatures have been used to describe this disease include spondyloepiphyseal dysplasia type Oman, dysostosis humero-cord and chondrodysplasia multiple dislocations. Recently, it has been proposed the general term skeletal dysplasia CHST3 gene related to refer to abnormalities bones and joints because of mutations in the gene CHST3.
This process is due to mutations in the gene CHST3, located on the long arm of chromosome 10 (10q22.1). This gene encodes a sulfotransferase 6-O-1 or C6ST-1 enzyme called chondroitin. This enzyme plays an important role in the development and maintenance of the skeleton. In particular, it is essential for the normal development of cartilage that makes up much of the skeleton in early development. The C6ST-1 proteoglycans modified enzyme chondroitin sulfate, which are abundant in cartilage tissue and give this consistency. The C6ST-1 enzyme performs a process known as sulfation. Specifically, the enzyme takes sulfate from a molecule called 3'-5'-phosphosulfate phosphoadenyl-(PAPS) and adds it to a specific location on proteoglycan chondroitin sulfate. Sulfation of these molecules is a critical step in cartilage formation.
They have identified at least 24 mutations in the gene responsible for skeletal dysplasia CHST3 related CHST3 gene. Most mutations change amino acids in the enzyme C6ST-1. Other coding mutations cause an abnormally short version of the enzyme. Each of these genetic changes reduces or eliminates the activity of C6ST-1, preventing the transfer of sulfate groups chondroitin sulfate proteoglycans. Defective sulfation of these molecules alters the normal development of cartilage and bone, resulting in short stature, joint dislocations, and other characteristics related to the disease.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with skeletal dysplasia CHST3 related gene, by PCR amplification of complete exons CHST3 gene, 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).