Seudoinflamatoria Sorsby fundus dystrophy (Fundus Dystrophy, Sorsby of pseudoinflammatory) - Gen TIMP3.
The fundus dystrophy seudoinflamatoria Sorsby is a disorder characterized by loss of central vision of subretinal neovascularization and ocular tissues atrophy. Affected individuals develop night blindness in the third decade of life and loss of vision choroidal neovascularization in the fourth or fifth decade. Fundus in drusen and subretinal yellowish material may occur. Overall, exudative macular degeneration develops in the patient 's eye within 6 months to 6 years. Signs and symptoms of the disease may include edema, macular hemorrhage, pigmentation and atrophy with chorioretinal atrophy.
This process is due to mutations in the TIMP3 gene, located on the long arm of chromosome 22 (22q12.3). This gene belongs to the family of genes and encoding TIMP tissue inhibitor of metalloproteinase-3. The proteins encoded by this gene family are inhibitors of matrix metalloproteinases, a group of peptidases involved in degradation of extracellular matrix (ECM). The expression of this gene is induced in response to mitogenic stimulation and this protein contains the domain of netrin which locates in the ECM.
Several mutations have been identified in the TIMP3 gene in people with seudoinflamatoria Sorsby fundus dystrophy. It is believed these mutations alter the function of tissue inhibitor of metalloproteinase-3, which can cause these mutations lead to abnormal subretinal deposit altering the balance between the accumulation and degradation of extracellular matrix. This could be because the subretinal deposit acts as a diffusion barrier to the entry of sufficient vitamin A photoreceptor.
This disease is inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for alteration is expressed. In most cases, an affected person has a parent with the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with seudoinflamatoria fundus dystrophy Sorby, by complete PCR amplification of the exons of the TIMP3 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).