Huntington-like types 1, 2 and 4, disease ..., (HLD1; HLD2; HLD4: Huntington disease-like types 1, 2 and 4) - Genes PRNP, JPH3 and TBP.
Syndrome , Huntington's disease-like (HDL: Huntington-like disease) is a disorder that resembles Huntington's disease. They described four syndromes HDL (HDL1, HDL2, HDL3 and HDL4). In all progressive brain disorders characterized by the manifestation of uncontrolled movements, emotional problems and loss of reason, occurring in people with the characteristics of the enfernmedad Huntington occur, but do not have their own mutations Huntington's disease.
HDL1, HDL2 and HDL4 usually occur at the beginning of adulthood, or half of it, though sometimes appear earlier. Early symptoms include irritability, emotional problems, involuntary movements, poor motor coordination, and problems learning or decision making. As the disease progresses, abnormal movements become more pronounced and can present problems in gait, speech or swallowing. Survival from the onset of symptoms may be a few years to over a decade. HDL3 begins much earlier in life, about 3 or 4 years. Children show a decline of reason, difficulty of movement, speech, and seizures.
These syndromes are rare, less common than Huntington's disease that affects between 3 and 7 per 100,000 people. The most common is HDL4, followed by HDL2 (almost exclusively African origin). HDL1 has only been described in a family, and HLD3 only two families from Saudi Arabia.
The affected genes, where changes occur, are different according to the syndrome. In HDL1 found PRNP gene alterations; HDL2 in JPH3 gene, and in the TBP gene HDL4. The mutation affecting HDL3 is not known. These PRNP, JPH3 and TBP genes encoding important for the development of normal brain function proteins. Alterations of any of these genes cause similar alterations. Mutations that appear increase the length of DNA repeated segment of these genes, resulting in a PRNP, JPH3 or abnormal protein TBP. This abnormal protein occurs in nerve cells (neurons) and alter its function. Dysfunction or death of neurons in certain brain areas causing the signs and symptoms of HDL syndromes.
HDL1, HDL2 and HDL4 have an autosomal dominant inheritance, ie altered in each copy cell causes the disease. Affected inherit the mutation from one parent affected. As is transmitted to offspring, can increase in length DNA fragment repeated, making signs and symptoms become severe. HDL3 appears to be autosomal recessive, implying that both gene copies of each cell must have the mutation. Each parent would have only one copy of the mutated gene and not show signs or symptoms of the disease.
Tests in IVAMI: IVAMI performed in the PCR amplification of any of these genes: PRNP (own HDL1), JPH3 (own HDL2) and / or TBP (own HDL4). However, given that HDL2 is almost exclusively African origin, HDL1 described in one family, and HDL3 described only in two families and little is known about its genetic basis, we recommend starting the genetic study only for study TBP (own HDL4) gene, while it is the most common process, unless some other circumstance advise another strategy.
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).