Costeff syndrome – OPA3 gene
Costeff syndrome, also known as autosomal recessive optic atrophy type 3 or 3-methylglutaconic aciduria type III (MGA III), is a disorder characterized by loss of vision, movement problems and intellectual disability. People with Costeff syndrome have degeneration of the optic nerve from the beginning of childhood (between birth and 6 years) or onset of childhood (between 6 and 12 years), manifesting a progressive loss of vision. Some affected people have nystagmus and strabismus. In addition, people with this syndrome develop problems with movement in late childhood that include spasticity, ataxia and coreiform movements. As a consequence of these movement difficulties, people with Costeff syndrome may require a wheelchair. On the other hand, although some people with Costeff syndrome have mild or moderate intellectual disability, others have a normal cognitive ability.
Costeff syndrome belongs to a group of metabolic disorders associated with a higher concentration of 3-methylglutaconic acid in the urine. The amount of this acid in the urine may contribute to the diagnosis of this syndrome, although this finding does not seem to influence the signs and symptoms of this disorder. This process is due to mutations in the OPA3 gene (OPA3: outer mitochondrial membrane lipid metabolism regulator), located on the long arm of chromosome 19 (19q13.32), which encodes a protein found in mitochondria. Although the exact function of this protein is unknown, it is believed to be involved in the regulation of the shape of mitochondria.
At least five mutations in the OPA3 gene have been identified in individuals with Costeff syndrome. Mutations in the OPA3 gene lead to a loss of OPA3 protein function. A particular genetic mutation in the Iraqi Jewish population (143-1G> C) alters the way in which the protein is encoded, which translates into an absence of functional protein. Cells without any functional OPA3 protein have abnormal mitochondria. These cells probably reduce energy production and die earlier than normal, decreasing the availability of energy in body tissues. It is not clear why the cells that control vision and movement are particularly affected.
Costeff syndrome is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Costeff syndrome, 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).