Bloom syndrome ... (Bloom syndrome) - Gen BLM
Bloom syndrome is an inherited condition characterized by marked genetic instability associated with short stature, facial erythema photosensitive telangiectásico, increased susceptibility to infection and cancer predisposition.
Affected individuals have skin that is sensitive to sun exposure, and usually develop a patch of red skin across the nose and cheeks, although rashes may appear in other areas that are normally exposed to the sun like the backs of the hands and forearms. In addition, telangiectasias usually appear in the rash and sometimes eyes. Other features include hypopigmentation or cutaneous hyperpigmentation in skin areas that are not exposed to sunlight. People with Bloom 's syndrome have an increased risk of any cancer and a predisposition to develop it at an earlier age than the general population.
Individuals with Bloom syndrome have distinctive facial features including a long, narrow face, a small lower jaw and a prominent nose and ears. Other features may include learning problems, an increased risk of diabetes, chronic obstructive pulmonary disease (COPD) and mild abnormalities of the immune system leading to frequent infections of the upper respiratory tract, ears and lungs during childhood. In addition, men with Bloom's syndrome usually do not produce sperm and are infertile as a result. Affected women generally have reduced fertility and have menopause at an earlier age than usual.
This process is due to mutations in the gene BLM (Bloom syndrome RecQ helicase like), located on the long arm of chromosome 15 (15q26.1). This gene encodes a protein synthesis Family RecQ helicase. Helicases are enzymes that bind to DNA and the two strands unwound coiled DNA molecule. This unwinding is necessary for various processes in the cell nucleus, including copying of DNA in preparation for cell division and repair of damaged DNA. When a cell prepares to divide, DNA is copied up chromosomes so that each new cell has two copies of each chromosome, one from each parent. The DNA copy of each chromosome is arranged on the sister chromatids, which are joined to one another during the early stages of cell division. Sister chromatids occasionally exchanged small sections of DNA during this time, a process called sister chromatid exchange. It is believed that these exchanges may be a response to DNA damage during the copying process. BLM protein helps avoid excessive exchange of sister chromatids and also participates in other processes that help maintain the stability of DNA during the copying process.
They have identified more than 70 mutations of the BLM gene in people with Bloom syndrome. A particular genetic mutation is responsible for almost all cases of Bloom syndrome among people of Central and Eastern European Jewish ancestry (Ashkenazi). This mutation eliminates six nucleotides and replaces them with other seven in position 2281 (2281 6ins7 delta, or blmAsh). The blmAsh mutation results in the synthesis of an abnormally short, nonfunctional version of the BLM protein. Other mutations BLM gene change amino acids in the protein sequence or create an early signal stop coding. These mutations also reduce the amount of functional protein BLM. As a result of the absence or deficiency of functional protein BLM, exchange frequency of sister chromatids it is about 10 times higher than the average. DNA exchange between the chromosomes derived from the mother and father of the person are also increased in people with mutations BLM gene. In addition, chromosome breakage occurs more frequently in affected individuals. All these changes are associated with gaps and breaks in the genetic material that disrupt the normal activities of the cells and cause health problems associated with this syndrome. BLM without the protein, the cell is less able to repair the damage caused by ultraviolet light DNA, resulting in increased sensitivity to sunlight. Moreover, these genetic changes allow cells divide uncontrollably resulting in a predisposition to cancer development.
Bloom syndrome is inherited in 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 detection of mutations associated with Bloom's syndrome, by complete PCR amplification of the exons of the BLM gene, 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).