Huntington's Disease ...; Huntington's chorea (Huntington disease) - Gen HTT (IT15, HD)

Huntington's disease is a progressive brain neurodegenerative process that causes uncontrolled movements, emotional problems, and loss of recognition. The most common form of the disease called Huntington adult - onset disease (Adult-onset Huntington disease), usually manifests around 30 or 40 years old and is characterized by uncontrolled movements, emotional disturbances and loss of ratiocination . Early signs and symptoms may include irritability, depression, discrete involuntary movements, poor coordination and problems to acquire new knowledge or to make decisions. Many affected by Huntington's disease develop involuntary movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have difficulty walking, talking or swallowing. Individuals with adult onset form of Huntington's disease usually live 15 to 20 years after the onset of early signs and symptoms.

A less common form of Huntington's disease known as juvenile form begins in childhood or adolescence. In addition to the characteristics of the adult - onset form, 30% to 50% of affected children have seizures. Juvenile Huntington's disease tends to progress faster than adult - onset form. Affected individuals usually live 10 to 15 years after the onset of early signs and symptoms.

This disease is due to mutations in the HTT gene, located on the short arm of chromosome 4 (4p16.3). This gene encodes a "huntingtin" protein called, whose precise function is unknown, but it is considered involved in the function of brain cells by transmitting signals, transporting molecules, or protecting from apoptosis. The HTT gene has in its 3'repeated triplet sequence CAG (cytosine, adenine, guanine). Normally, there are 10 to 35 CAG triplet repeats in the sequence.

Hereditary mutation responsible for Huntington's disease, known as an expansion of CAG trinucleotide repeat, increases the size of the segment in the HTT gene CAG. As a result, in patients with Huntington 's disease the number of repeats can be from 36 to over 120 (mean 44). People who own between 36 and 40 CAG triplet repeats may develop or not develop the disease, and those over 40 almost always develop. Increasing the size of the CAG repeat sequence results in production of a protein (huntingtin) excessively long. This elongated protein is fractionated into smaller fragments that form complexes with each other, accumulating within neurons, altering their function and causing the eventual death of the cells containing them , leading to the signs and symptoms of this disease.

Huntington's disease has an autosomal dominant, which means that a single copy of the gene altered in each cell is sufficient to express the disease. Typically, the disease is inherited from an affected parent, but described a small percentage (approximately 3%) without affected parent, in which case the process is due to the emergence "de novo" mutations. A characteristic of this type of alteration is the "advance" consisting increased repetitions of the CAG triplet as the gene to new generations of descendants is transmitted, thereby "advance" in the time of the signs and symptoms of the disease. This is due, to a CAG more triplets is inversely associated with age at onset of manifestations, being smaller the greater the number of repetitions. Thus, developing manifestations in adulthood usually have 40 to 50 repetitions, while patients who develop early usually have in the HTT gene over repeated 50 or 60 triplets. Those with 27 to 35 repetitions do not develop the process but have the risk that their offspring suffer by increasing repetitions to be transmitted to other generations.

Tests in IVAMI: detecting the number of CAG triplet repeat is of interest to confirm a clinical diagnosis in people with signs and symptoms, and also for predicting the possible involvement of descendants. In IVAMI we detect the number of repetitions of the sequence CAG expansion in the HTT gene by complete PCR amplification and 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).