Atrophy dentatorubro-pallidoluysian (Dentatorubral-pallidoluysian Atrophy -DRPLA-) - Gen ATN1
The dentatorubro-pallidoluysian atrophy (DRPLA: Dentatorubral-pallidoluysian Atrophy) is a progressive neurodegenerative disease, autosomal dominant, manifested by involuntary movements, mental and emotional problems, and loss of reason. The average age of onset is 30 years, but can vary greatly, from a start in early childhood until after 60 years. Signs and symptoms of DRPLA differ from children to adults. Before age 20, those affected have myoclonic movements, contractures, changes in behavior, intellectual disability, physical stability problems and motor coordination (ataxia). After 60 years, most often ataxia and uncontrolled movements (choreoathetosis), psychiatric symptoms, and intellectual impairment (dementia).
This disease is caused by mutation of the gene ATN1, located on the short arm of chromosome 12 (12p13.31). This gene encodes the "atrophin-1" protein, which plays an important role in neurons in many areas of the brain. It is believed that atrophin-1 can act as a transcriptional co-repressor, which means that interacts with other proteins binding DNA to suppress the activity of certain genes, but can not bind to DNA by itself. A ATN1 region gene segment containing a trinucleotide repeat CAG. This segment consists of a series of amino acids (cytosine, adenine and guanine) which appear several times in a sequence. In most people, the number of CAG repeats in the gene ATN1 is 6 to 35.
The mutation responsible for the development of the disease is in an area CAG trinucleotide repeat. The length of such alleles will, as a result of repetitions of the CAG triplet Variable. In patients DRPLA, the number of repetitions of the triplet is at least 48 times, and thus repeated gene region may have two to three times the normal length. This repeat changes the structure of the "atrophin-1" protein. This altered protein accumulates in the neurons, and interferes with normal cellular functions, dysfunction, and eventual death of these neurons, causing uncontrolled movements, intellectual decline, and other disease characteristics.
Its autosomal dominant inheritance means that a single copy altered in every cell, is sufficient to express gene involvement. In most cases, those affected have a parent with the disease. As the ATN1 altered gene is passed from one generation to the next, the length of the sequence triplet CAG repeated often increases, and repeats often associated with earlier onset of signs and symptoms (early), which in it is increasingly evident when the altered gene is inherited from the father.
Tests in IVAMI: IVAMI performed in detecting the number of repetitions of the CAG triplet in ATN1 gene. To do this, we amplified by PCR, the ATN1, and then proceed to gene 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).