Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Leber 's hereditary optic neuropathy (Leber hereditary optic neuropathy -LHON-) - Genes MT-ND1, MT-ND4, MT-ND4L, MT-ND6 and other mitochondrial genes in which mutations have been described (MT-ND2, MT-ATP6 , MT-ND5 or other).

The Leber's hereditary optic neuropathy (LHON: Leber Hereditary optic neuropathy) is an inherited form of vision loss, which usually manifests in the second or third decade of life, although sometimes it manifests itself in extreme ages of life. The disease affects men more than women.

The first symptoms are blurred vision, unilateral or bilateral start, but eventually affects both eyes and worsens with loss of visual acuity and color vision. The loss of vision is motivated by the death of neurons that send the information from the eye to the brain (optic nerve). The process has the unique in this process, characteristic of being painless. Although central vision gradually improves in a small percentage of cases, in most cases, vision loss is deep and permanent. Loss of vision is usually the only symptom of LHON. There is a process called LHON-plus in addition to vision loss and motor electrical conduction which controls the heartbeat changes occur. Some affected individuals develop characteristics similar to multiple sclerosis, such as muscle weakness, poor coordination, numbness, and other health problems.

The disease is motivated by mutations that can occur in several mitochondrial DNA genes: (. 956 nt) MT-ND1, MT-ND4 (1378 nt.), MT-ND4L (297 nt.) And MT-ND6 (525 nt. ). Each of these genes encodes a protein involved in mitochondrial function (NADH dehydrogenase 1 NADH dehydrogenase 4, NADH dehydrogenase and NADH dehydrogenase 4L 6, respectively). These proteins are part of a large enzyme complex mitochondrial energy producer, and when altered, upon mutation, altered mitochondrial function. In addition, mutations in these genes can increase production within the mitochondria of reactive oxygen species. It is not clearly known how neurons specifically affects the optic nerve. It is known that a fairly significant percentage of people with some of the mutations described in these genes do not develop the disease, so there must be additional factors that determine a person develops signs and symptoms of the process. These factors have been considered to smoking, alcohol intake or the effect of other genes linked to chromosome X. Specifically, over 50% of men with a mutation and more than 85% of women with a mutation not They have loss of vision or related health problems.

Several mutations have been identified in the MT-ND1, MT-ND4, MT-ND4L and MT-ND6 genes in people with Leber 's hereditary optic neuropathy. A common mutation MT-ND1 is responsible for approximately 13% of all cases. This mutation replaces guanine nucleotide by adenine at position 3460 of the gene (G3460A). This change is associated with moderately severe cases of Leber's hereditary optic neuropathy. However, between 20% and 40% of people with vision loss due to this mutation have some recovery of vision. Meanwhile, mutations in the MT-ND4 gene each change in a single amino acid dehydrogenase protein NADH 4. MT-ND4 mutation is the most common cause of optic neuropathy Leber hereditary, being responsible for about 70% of all cases worldwide. This mutation (G11778A or Arg340His) replaces the amino acid arginine amino acid histidine at position 340. This altered protein tends to cause severe vision loss, with little chance of recovery.

Regarding MT-ND4L, gene mutation has been identified in several families affected, T10663C or Val65Ala, replacing the amino acid valine at the amino acid alanine at position 65 in NADH dehydrogenase 4L protein. In the MT-ND6 gene, each of the mutations identified change in a single amino acid dehydrogenase protein NADH 6. MT-ND6 common mutation is responsible for about 14% of all cases of Leber 's hereditary optic neuropathy, and the most common cause of this process in people of French Canadian descent. This genetic change, or Met64Val T14484C replaces the amino acid methionine amino acid valine at position 64. This mutation is associated with good long - term prognosis; people affected with this genetic change have a probability of 37 to 65% of certain visual recovery.

The disease has a mitochondrial inheritance pattern, also known as maternally inherited characteristic feature of mitochondrial genes. This is because they are the maternal oocytes, and no paternal sperm mitochondria contributing in embryonic development, and therefore women transmit this mitochondrial disorder to their children. The alteration may appear in every generation and can affect both men and women, but not men parents transmit to their children.

Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with hereditary optic neuropathy Leber, by complete PCR amplification of the exons of the MT-ND1, MT-ND4, MT-ND4L and MT-ND6 genes, respectively, and subsequent sequencing. They can also studied other genes in which mutations have been described less frequently (MT-ND2, MT-ATP6, MT-ND5, or other), by sequencing of each.

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).