Autosomal dominant optic atrophy and cataract (ADOAC) - OPA3 gene

Autosomal dominant optic atrophy and cataract (ADOAC) is an ocular disorder characterized by a decrease in visual acuity, with varying severity from near normal vision to complete blindness. The decrease in visual acuity arises as a result of the loss of retinal ganglion cells, atrophy of the optic nerve and formation of cataracts. This ocular anomaly can develop at any time, but it usually appears in childhood. Other frequent eye problems in this disease include nystagmus or color vision deficiency. In addition, other signs and symptoms related to this process may include optic nerve neuropathy, which in turn can cause cerebellar ataxia, gait instability, paresthesias in the arms and legs, spasticity or tremors. In some cases affected people develop deafness neurosensory.

ADOAC is due to mutations in the OPA3 gene (outer mitochondrial membrane lipid metabolism regulator), located on the long arm of chromosome 19 (19q13.32), which encodes a protein found in mitochondria. It is believed that this protein is involved in the regulation of the shape and structure of mitochondria, and in apoptosis or cell death.

At least, four mutations in the OPA3 gene have been described in individuals with ADOAC. The identified mutations occur in a copy of the gene in each cell. A mutation that has been found in several people replaces the amino acid glutamine for the amino acid glutamic acid at position 105 of the protein (Gln105Glu or Q105E). This and other mutations give rise to an abnormal mitochondrial function. Mitochondria become deformed and disorganized, and their ability to produce energy decreases. As a consequence, the cells that contain these mitochondria appear to be more susceptible to apoptosis, particularly those with high energy demands, such as retinal ganglion cells. Loss of retinal ganglion cells and optic nerve atrophy contribute to vision impairment. It is likely that nerve cells in other parts of the body are similarly affected by dysfunctional mitochondria, which causes problems with movement and hearing loss in some people with this condition.

ADOAC is inherited with an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the process. In most cases, an affected person has an affected parent.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with autosomal dominant optical atrophy and cataract (ADOAC), by means of the complete PCR amplification of the exons of the OPA3 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).