Neuropathy, ataxia and retinitis pigmentosa (NARP) - MT-ATP6 gene.
Neuropathy, ataxia and retinitis pigmentosa (NARP), also known as NARP syndrome, is a process that mainly affects the nervous system characterized by sensory neuropathy, muscle weakness and ataxia.
Many affected individuals also have vision loss caused by changes in the retina. In some cases, it results in retinitis pigmentosa which causes loss of vision. Other signs and symptoms of the disease include learning problems; developmental delays; development of dementia in the elderly; seizures; hearing loss; and cardiac conduction defects. These signs and symptoms vary among affected individuals.
This process is due to mutations in the MT-ATP6 gene (mitochondrially encoded ATP synthase membrane subunit 6), located in the mtDNA (mitochondrial DNA), which encodes an essential protein for normal mitochondrial function. Through a series of chemical reactions, mitochondria use oxygen and simple sugars to generate adenosine triphosphate (ATP), the cell's main source of energy. The protein forms a subunit of an enzyme called ATPsintase, which is responsible for the last step in the production of ATP.
A small number of mutations in the MT-ATP6 gene responsible for the development of this process have been identified. Each of these mutations changes a nucleotide in the gene. The most frequent genetic change replaces thymine with guanine at position 8993 (T8993G). Mutations alter the structure or function of ATP synthase, leading to a reduction in the ability of mitochondria to produce ATP. Although the precise effects of these mutations are not clear, it is still analyzed how changes in the MT-ATP6 gene interfere with ATP production and cause muscle weakness, loss of vision, and the other characteristics of NARP.
This disease is inherited with a mitochondrial or maternal inheritance pattern. This inheritance pattern applies to genes contained in mitocondrial DNA. Mitochondrial processes can appear in every generation of a family and can affect both men and women. The severity of some mitochondrial processes is related to the percentage of mitochondria in each cell that has a particular genetic change. Most individuals with NARP have a specific mutation in 70 to 90 percent of their mitochondria. When this mutation is present in a higher percentage of mitochondria (90 to 95 percent), it causes a more serious disease known as Leigh syndrome of maternal inheritance. Because these two processes are due to the same genetic changes and may appear in different members of the same family, it is thought that they may represent a range of characteristics rather than two different overlapping syndromes.
Tests performed in IVAMI: in IVAMI we detect mutations associated with neuropathy, ataxia and retinitis pigmentosa (NARP), by means of complete PCR amplification of the exons of the MT-ATP6 gene, and their subsequent sequencing.
Recommended samples: blood taken with EDTA for separation of blood leukocytes, or card impregnated with dried blood sample (IVAMI can mail the card to deposit the blood sample).