Cones-S, Increased ..., Goldmann-Favre syndrome (Enhanced S-Cone syndrome, Goldmann-Favre syndrome) - Gen NR2E3.

Syndrome Goldmann-Favre (SFM), also referred to increase cone-S, is a vitreoretinal dystrophy characterized by early onset of night blindness, decreased bilateral visual acuity, and progressive degenerative changes in pigmentation, macular edema and retinoschisis .

In general, the onset of the syndrome occurs in childhood, manifesting with progressive loss of visual acuity and night blindness. Other signs and symptoms of the disease include decreased peripheral vision, cataracts and optic atrophy. Degenerative changes are glassy and may include microfibrillar filaments, liquefaction and posterior vitreous detachment. The characteristics of the fundus include changes in pigmentation ring (mass deposits pigment), central or peripheral retinoschisis and cystoid macular edema. GFS characteristics are generally bilaterally symmetrical. The electroretinogram is abnormal: ERG both of the rods and the cones decreases greatly and can not reach appreciable. Patients may have a greater sensitivity to blue light because of the increased sensitivity of S. cones In most cases, visual loss occurs in the first two decades of life.

This process is due to mutations in the NR2E3, located on the long arm of chromosome 15 (15q23). This gene encodes a nuclear receptor of the retina that is involved in the differentiation of photoreceptors. This gene is part of a large family of transcription factors involved in nuclear receptor signaling pathways. It has been shown that nuclear receptors regulate pathways involved in embryonic development and in maintaining proper cellular function in adults. Members of this family are characterized by discrete domains which function in DNA and ligand binding. This gene encodes a nuclear receptor of the retina is a factor ligand dependent transcription.

Mutations in the NR2E3 alter the genetic program that controls the proportions and topography of the three types of cones in the retina, leading to an abnormal pattern of photoreceptors. In some patients it has reported a total absence of canes. In all patients with mutations in the NR2E3 increased cone density normal type S occurs, generating a gain of function which results in greater sensitivity to blue light. Mutation identified in NR2E3 involves a change from aspartic acid to glycine at amino acid position 406 (p.D406G), which affects stability or nuclear receptor activity of the retina. Another R311Q mutation is identified.

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 Goldmann-Favre (GFS) syndrome or increased cone-S, by complete PCR amplification of exons NR2E3, 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).