Dysplasia SADDAN (SADDAN, severe achondroplasia with developmental delay and acanthosis nigricans) - Gen FGFR3.
SADDAN dysplasia (severe achondroplasia with developmental delay and acanthosis nigricans) is a disorder of bone growth characterized by skeletal abnormalities, brain and skin. Signs and symptoms of the disease include short stature with arms and particularly short legs, unusual inclination of the leg bones, small chest with ribs and curved clavicles, short and wide fingers, Extra folds of skin on the arms and legs. Structural abnormalities cause brain seizures, developmental delay deep and intellectual disability. Some affected individuals have apnea. In addition, individuals with this disease have acanthosis nigricans, progressive skin disorder characterized by the presence of a thick, dark, velvety skin that develops in infancy or childhood.
This disease is due to mutations in the FGFR3 gene, located on the short arm of chromosome 4 (4p16.3). This gene encodes a protein called receptor fibroblast growth factor 3. This protein is part of a family of receptors of fibroblast growth factor that share similar structures and functions. These proteins play a role in several important cellular processes, including the regulation of growth and cell division, determining the cell type, the formation of blood vessels, wound healing and embryonic development. The FGFR3 protein across the cell membrane, so that one end of the protein remains inside the cell and the other end remains on the outer surface. This positioning of the protein allows it to interact with specific growth factors outside the cell and receive signals that control growth and development. When these growth factors bind to the FGFR3 protein, protein triggers a cascade of chemical reactions within the cell that instruct to perform certain changes, such as maturation assume specialized functions. Several isoforms of the FGFR3 protein are encoded from the FGFR3 gene. Different isoforms are found in various tissues of the body and interact with a variety of growth factors. Many isoforms are found in the cells that form bones. It is believed that bone cells, the protein FGFR3 regulates bone growth by ossification, particularly in the long bones. One particular isoform of FGFR3 protein is specifically in epithelial cells, including the cells that form the epidermis.
It has identified a mutation in the FGFR3 gene in people with SADDAN dysplasia. Genetic change the amino acid methionine replaced by the amino acid lysine at position 650 of the protein (Lys650Met or K650M). It is believed that this mutation strongly Overactive the FGFR3 protein, leading to serious problems with bone growth. It remains uncertain how the mutation causes developmental delay and acanthosis nigricans.
SADDAN dysplasia is considered an autosomal dominant disorder because a mutated copy of the FGFR3 gene in each cell is sufficient to cause disease. The few reported cases of dysplasia SADDAN are due to new mutations in the FGFR3 gene and occur in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with dysplasia SADDAN, by complete PCR amplification of the exons of the FGFR3 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).