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


Myoclonic epilepsy with ragged red fibers (Myoclonic epilepsy ragged-red fibers With -MERRF-) - Genes MT-TK, MT-TL1, MT-TH, and MT-TS1.

Myoclonic epilepsy ragged red fibers with (MERRF) is a disorder that affects many parts of the body, especially the muscles and nervous system. In most cases, the signs and symptoms appear during childhood or adolescence. MERRF characteristics vary widely among affected individuals, even among members of the same family. This disease is characterized by myoclonus, myopathy and spasticity. Other features MERRF include epilepsy, ataxia, peripheral neuropathy and dementia. In addition, affected individuals may have hearing loss, optic atrophy, short stature and cardiomyopathy. Less often, people with MERRF develop lipomas, just below the surface of the skin.

This process is due to mutations in the MT-TK, MT-TL1, MT-HT and MT-TS1 genes. Mutations in the MT-TK gene are the most common cause of the disease, occurring in over 80% of all cases. A small percentage of cases MERRF are due to mutations in mitochondrial genes other and, in some cases the cause of the condition is unknown.

These genes located in mitochondrial DNA, encoding molecules called transfer RNA (tRNAHis, tRNALys, tRNALeu [UUR] and tRNASer [UCN], respectively). These molecules help synthesize proteins within mitochondria. These proteins carry out the steps of oxidative phosphorylation in mitochondria use oxygen, simple sugars and fatty acids to create adenosine triphosphate (ATP), the main energy source of the cell. Molecules encoded from these genes are involved in the assembly of proteins that carry out oxidative phosphorylation. In certain pancreatic cells, called beta cells, mitochondria play a role in controlling the amount of glucose in the blood. In response to high concentrations of glucose, mitochondria help trigger the release of insulin, which regulates blood sugar levels in the blood by controlling the amount of glucose passing blood cells to be converted into energy.

Most mutations responsible myoclonic epilepsy with ragged red fibers (MERRF) single nucleotide change in the gene. A common mutation in the MT-TK gene, is responsible for about 80% of all cases of MERRF. This genetic change adenine nucleotide replaced by guanine nucleotide at position 8344 of the gene (A8344G). The A8344G mutation impairs the ability of mitochondria to encode proteins, using oxygen and energy. Some people with mutations in the MT-TH, TM-TK and MT-TL1 genes have some characteristics of MERRF and some characteristics of other mitochondrial alteration called mitochondrial encephalomyopathy, lactic acidosis and stroke (MELAS) type episodes. These affected individuals are said to have an overlap syndrome MERRF / MELAS. Additional signs and symptoms of the syndrome include severe recurrent headaches, myopathy, ataxia, hearing loss and stroke - like episodes, including a loss of consciousness. The mutation in the MT-TK gene causing overlap syndrome MERRF / MELAS replaces thymine cytosine nucleotide by nucleotide at position 8356 of the gene (T8356C). In the MT-TH gene, the mutation involved in this overlap syndrome replaces guanine nucleotide by adenine nucleotide at position 12147 gene (G12147A). It is unknown why these mutations cause overlapping characteristics of MERRF and MELAS. Meanwhile, we have identified two mutations in the MT-TS1 gene in some people with variants myoclonic epilepsy ragged red fibers with (MERRF) forms. In these cases, affected individuals often express myoclonus, myopathy, ataxia, hearing loss, seizures and intellectual impairment. One of these mutations replaces the thymine nucleotide with the cytosine nucleotide at position 7512 of the gene (T7512C). The other mutation inserts an additional cytosine at position 7472 (7472insC). It is unclear how these genetic changes cause variant forms of MERRF.

Myoclonic epilepsy ragged red fibers with (MERRF) is inherited mitochondrial pattern, also known as maternal inheritance. This pattern of inheritance applies to genes contained in the mitochondrial DNA (mtDNA). Since egg cells, but not sperm cells contribute to developing embryo, only women transmit mitochondrial alterations to their children. Mitochondrial disorders can appear in each generation of a family and can affect both men and women, but parents do not pass mitochondrial traits to their children. In most cases, people with MERRF inherit an altered mitochondrial gene from his mother, who may or may not show symptoms of the disease. Less commonly, the disease results from a new mutation in a mitochondrial gene and occur in people with no family history of MERRF.

Tests in IVAMI: in IVAMI perform detection of mutations associated with myoclonic epilepsy with ragged red fibers (MERRF), by complete PCR amplification of the exons of the MT-TK, MT-TL1, MT-TH gene and MT- TS1, respectively, 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).