Hutchinson-Gilford progeria syndrome ... (Hutchinson Gilford progeria syndrome) - Gen LMNA
Progeria syndrome is Hutchinson-Gilford genetic alteration of childhood onset characterized by rapid acceleration of the natural aging process. Children usually appear normal at birth and in early childhood, but then suffer from stunting. These individuals develop a characteristic facial appearance that includes prominent eyes, a thin nose with a flat nose, thin lips, small chin and protruding pinnae. Other signs and symptoms may include additional alopecia, skin aging appearance, joint abnormalities and loss of subcutaneous fat. In addition, affected individuals have arteriosclerosis onset in childhood and are at increased risk of heart attack or stroke at a young age. These serious complications may worsen over time and are potentially fatal. This disease does not affect intellectual development or the development of motor skills such as sitting, standing and walking.
This process is due to mutations in LMNA (Lamin A / C), located on the long arm of chromosome 1 (1q22). This gene encodes several proteins called somewhat different laminae. The two main proteins encoded from this gene, lamin A and lamin C are encoded in most cells in the body and have a nearly identical amino acid sequence. Lamins A and C are structural proteins called intermediate filament proteins. Intermediate filaments provide stability and strength to the cells. Lamins A and C are support components of the nuclear envelope. Specifically, these proteins are found in nuclear lamina. The nuclear envelope regulates the movement of molecules between the inside and outside of the core and is likely to play a role in regulating the activity of certain genes. Protein lamin A must be processed within the cell before becoming part of the sheet. Its initial form called prelamina A, is subjected to a complex series of steps which are necessary for the protein is inserted into the sheet. Lamin C does not have to undergo this process before becoming part of the sheet.
It has identified a specific mutation in the LMNA gene in most patients with Hutchinson-Gilford progeria progeria of syndrome. This mutation replaces the nucleotide cytosine by thymine nucleotide at position 1824 (C1824T). This mutation is also known as Gly608Gly or G608G. The C1824T mutation results in an abnormal version of the protein lamin A progerina called, in which 50 amino acids are absent near one end. The location of this mutation does not affect the synthesis of lamin C. has identified other mutations in LMNA in a small number of people with the disease characteristics. Mutations in the gene give rise to an abnormal version of lamin A that can not be processed correctly within the cell. When the altered protein is incorporated into the film, it may alter the shape of the nuclear envelope. Over time, the accumulation of this protein altered appears to impair the structure and function of the nucleus, making cells more prone to premature apoptosis. Work is underway to determine how these changes cause signs and symptoms of the syndrome.
Progeria syndrome Hutchinson-Gilford is considered an autosomal dominant disease, which means that a copy of the altered gene in each cell is sufficient to express the disease. This disease is due to new mutations in LMNA and generally occurs in people with no history of disease in your family.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Hutchinson-Gilford progeria of syndrome by complete PCR amplification of the LMNA exons 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).