Familial partial lipodystrophy (Familial partial lipodystrophy) - Genes ADRA2A, AKT2, CIDEC, LIPE, LMNA, PLIN1 and PPARG
Familial partial lipodystrophy, also known as Köbberling Dunnigan-syndrome, is a rare disease characterized by abnormal fat distribution. Individuals with familial partial lipodystrophy, lack of adipose tissue in the arms, legs and hips, giving these parts of the body a very muscular. The fat can not be stored in these areas it accumulates around the face, neck and abdomen. Excess fat in these areas gives individuals a defined as "cushingoid," because it resembles the physical characteristics associated with Cushing's disease appearance. This abnormal fat distribution can start at any time from infancy to adulthood.
An abnormal accumulation of fat in the body can cause health problems in adulthood. Many people with familial partial lipodystrophy develop resistance to insulin, which can worsen to become diabetes mellitus. Some people with familial partial lipodystrophy nigricans develop a skin condition associated with high concentrations of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds thicken, become dark and velvety. Most people with familial partial lipodystrophy also have hypertriglyceridemia, which can cause pancreatitis. Moreover, family partial lipodystrophy can also lead to hepatic steatosis, which can cause hepatomegaly and abnormal liver function. After puberty, some women with ovarian cysts develop multiple, hirsutism, and infertility.
They have been described at least six forms of familial partial lipodystrophy, which are distinguished by their genetic cause. The most common form, called Type 2 or Dunnigan disease is due to mutations in LMNA (Lamin A / C). In this way, in addition to the signs and symptoms described above, some people develop myopathy, cardiomyopathy, coronary artery disease and problems with conduction system.
We found several mutations in LMNA responsible for familial partial lipodystrophy type 2 LMNA (Lamin A / C), located on the long arm of chromosome 1 (1q22), encoding two similar proteins: lamin A and lamin C. These proteins have a nearly identical amino acid sequence. These proteins are structural proteins called intermediate filament proteins. Intermediate filaments provide stability and strength to the cells. Specifically, these proteins are found in the nuclear lamina, a mesh - like intermediate filament and other proteins that bind to the inner membrane of the envelope layer. Protein lamin A must be processed within the cell before becoming part of the sheet. Its initial form called prelamin A, is subjected to a complex series of steps necessary for the protein is inserted into the sheet. Lamina C does not have to undergo this process before becoming part of the sheet.
Although the effects of mutations LMNA gene in adipocytes are not well understood, it is believed that these mutations can weaken the nuclear envelope, which ultimately causes premature death of these cells causing the body can not store and properly metabolize The fats. These anomalies adipose alter hormone production and affects many organs of the body. However, it is unclear why the changes make you lose fat in some parts of the body is stored abnormally in others.
Other less common forms of the disease are due to mutations in different genes:
- ADRA2A gene (alpha adrenoceptor 2nd), located on the long arm of chromosome 10 (10q25.2)
- AKT2 gene (AKT serine / threonine kinase 2), located on the long arm of chromosome 19 (19q13.1-q13.2)
- Familial partial lipodystrophy type 3 (FPLD3) due to mutations in the gene PPARG (peroxisome proliferator activated receptor gamma), located on the short arm of chromosome 3 (3p25).
- Familial partial lipodystrophy type 4 (FPLD4) due to mutations in the gene PLIN1 (perilipin 1), located on the long arm of chromosome 15 (15q26).
- Familial partial lipodystrophy type 5 (FPLD5) due to mutations in the CIDEC (cell death inducing DFFA like effector c) gene, located on the short arm of chromosome 3 (3p25.3)
- Familial partial lipodystrophy type 6 (FPLD6) due to mutations in the gene LIPE (E lipase, hormone sensitive type), located on the long arm of chromosome 19 (19q13.2)
LMNA and other genes associated with familial partial lipodystrophy encode proteins with a variety of functions including important roles in fat storage. In particular, these proteins play important roles in the development and function of adipocytes. Mutations in any of the genes associated with familial partial lipodystrophy reduce or eliminate the function of their respective proteins, which alters the development, the structure or function of adipocytes and causes the body can not properly store and use fat. These anomalies adipose tissue alter hormone production and affects many organs of the body. However, it is unclear why changes cause fat lost in some parts of the body and stored abnormally in others. In some people with familial partial lipodystrophy, they have not identified genetic mutations.
Most cases of familial partial lipodystrophy, including type 2 are inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the disease. In some cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family. Rare cases of familial partial lipodystrophy the seem to run with an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform the detection of mutations associated with familial partial lipodystrophy, by complete PCR amplification of the exons of the ADRA2A, AKT2, CIDEC, LIPE, LMNA, PLIN1 and PPARG genes, respectively, 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).