Introduction Leukocyte adhesion deficiency type 1 (OMIM # 116920) (LAD1) is a rare (1 in every 10,000 live births) autosomal recessive syndrome resulting from mutations in the gene encoding CD18 protein (the integrin beta 2 chain, ITGB2). ITGB2 has 16 exons located on 21q22.3. This gene is involved in adhesion and transmigration of human leukocytes in vivo, and thus patients with LAD1 have absent or severely reduced expression of ITGB2 chain on the surface of their leukocytes resulting in impaired accumulation of myeloid leukocytes at extravascular sites. The product of this gene belongs to the integrin beta chain family of proteins. A given chain may combine with multiple partners, resulting in different integrins. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. Integrins are known to participate in cell adhesion as well as cell-surface mediated signaling. LAD1 is characterized by recurrent bacterial and fungal infections, skin ulcers with slow wound healing, periodontitis, sepsis and otitis media due to the blockade of leukocyte migration in place of inflammation and impaired pus formation. Infections affecting the skin, respiratory tract, bowel, and perirectal areas are usually apparent from birth onward [12]. Infections affecting the skin, respiratory tract, bowel, and perirectal areas are usually apparent from birth onward [12]. The molecular basis for CD18 deficiency varies. Severe and moderate forms of LAD1 are caused by different ITGB2 mutations resulting in aberrant beta mRNA and/or protein [5-8]. However, leukocytosis, periodontal disease, and delayed wound healing are still very significant clinical features. Early diagnosis should be considered in any patient with recurrent ... ... middle of paper ... ...GB2 can be identified by increasing the number of LAD1 patients. Since the prediction tools had different results, more development is needed for these tools. Variant dependent methods vary, in their ability to predict the effect of a variant on gene or protein function. Some are highly predictive. Others are at best suggestive, or circumstantial. However, Functional studies can be addressed to better understanding and interpretation of variation and their effects on function and stability of the protein. Understanding the structure and the biology of the genome as well as understanding the biology of the disease could result in advances of the science of medicine and improving effectiveness of health care in patients. Finally, Identifying gene mutations may play an important part in choosing the right method to perform gene therapy for LAD1 patients in the future.
Marfan syndrome is an inherited disorder that affects the connective tissue of the body (“What is Marfan Syndrome?” n.d.). The connective tissue plays a vital role in supported the tendons, heart valves, cartilage, blood vessels, and more parts of the body (“Connective Tissue,” n.d.). “What is Marfan Syndrome?” (n.d.) explains that the condition has no cure, and those who have it lack strength in their connective tissue, affecting their bone, eyes, skin, nervous system, and lungs. Furthermore, Marfan syndrome is common, and it is imperative to understand how the body is affected by it, the symptoms, and the treatment of this condition.
There are more than ten inherited disorders within Elhers-Danlos syndrome. Ehlers-Danlos syndrome (EDS) is a “genetic defect in collagen and connective tissue synthesis and structure” (Schwartz, 2013). EDS affects the skin, joints and blood vessels in most types. In EDS the abnormality of the collagen varies dependent on the type of EDS. Six of the main types of Ehlers-Danlos syndrome include; types I and II EDS which are called the classic type, type III hypermobile EDS, type IV vascular EDS, type VI kyphoscoliosis EDS, type VII A and B arthrochalasia EDS, and type VII C dermatosparaxis EDS (Willacy, 2011).
EDS can vary in severity and are transmitted as autosomal recessive, autosomal dominant, or X-linked recessive traits. The primary characteristics are hyperextensible skin and joints (Dia. 1-2, pg.6), tendency to bruise easily (Dia. 3, pg.6), reduced wound healing capability, pseudotumors, and ocular defects. Differences within the six types may reflect inter/intra familial variability or genetic heterogeneity. Each type of EDS is classified symptoms and signs that are resulted (Clarke, D., Skrocki-Czerpak, K., Neumann-Potash, L).
Faries, D. E., Houston, J. P., Sulcs, E. N., & Swindle, R. W. (2012). A cross-validation of the provisional diagnostic instrument (PDI-4). BioMed Central, 13(1), 104. doi:10.1186/1471-2296-13-104
X-linked Agammaglobulinemia, or XLA for short, was the first immunodeficiency disease ever to be discovered. Ogden C. Bruton, the man who discovered it, was studying an eight-year-old boy in 1952 who had very confusing symptoms. He studied the boy for almost four years and was still confused by the randomness of his symptoms. The boy was getting many infections in these four years and Bruton could not figure out why until he decided to investigate the boy’s blood. He found that the boy was not producing the correct antibodies to fight off infection. After further research, Bruton was able to relate the symptoms back to the child’s genes. Long after Bruton had passed, the disease was studied in depth and found to be an X-linked genetic disorder effecting the antibody production in males. It was then named X-linked Agammaglobulinemia or, in memory of Ogden Bruton, Bruton’s X-linked Agammaglobulinemia.
Marfan syndrome is a Single Gene Mutation and the gene that is mutated is FBN 1 (Fibrillin 1).The gene is located on chromosome 15 and the disorder’s mode of inheritance is autosomal dominant. This means that females and males are equally affected and that only one gene, “abnormal” gene is needed from either parent to be inherited in. Fibrillin 1 basically affects the elasticity of connective tissue. The gene makes many fibrillin proteins and these fibrillin proteins then join together to form a long, and string like object called microfibrils.
Makover, M. & Zieve, D. (2011, February 14). Systemic Lupus Erythematosus. National Center for Biotechnology Information. Retrieved July 14, 2012, from http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001471/
The fibronectin which is a ligand for fibronectin-binding protein expressing bacteria binds to the integrins, expressed by the inflamed endothelial cells, causing increased adhesion susceptibility , tissue necrosis, inflammation and vegetation growth.
The disease is found in a mutation on the HEXA gene. The HEXA gene makes beta-Hexosaminidase A, an enzyme that is necessary for proper spinal cord and brain development. This works to break down GM2 ganglioside, a fatty substance. When a mutation occurs here, the GM2 ganglioside can’t be broken down, accumulating to harmful levels in neurons of the brain and spinal cord, which results in the damaging symptoms of the disease.
Marfan syndrome is an autosomal dominant disorder resulting from mutations in the gene fibrillin-1 (FBN1) found on chromosome 15 (McKusick V, O'Neill M, 2013). At least 140 different mutations of this gene have been recorded since 2008 (Frey R, Lutwick L, 2009). The FBN1 gene regulates the manufacturing of the fibrillin-1 protein that assists in constructing fibrous filaments which are present in portions of the fibers in connective tissue (Frey R, Lutwick L, 2009). Those filaments manage the discharge of growth factors or protein molecules which prompt the reproduction and growth of cells (Frey R, Lutwick L, 2009). In healthy individuals, the filaments discharge growth factors at the right moment but those who have Marfan syndrome are faced with the dilemma of growth factors being discharged too soon. The early release of growth factors results in fragile connective tissue and the uncommonly lengthy limbs of those with the disorder.
Tamparo, C. D. & Lewis, M. A. (2011). Diseases of the human body. Philadelphia, PA: F.A. Davis Company.
This disease is caused by a defective gene and was discovered in the 1930's. Scientists are
Sex-linked disorders only affect males and are passed down through female carriers. A boy inherits the disorder when he receives an X chromosome with a mutated dystrophin gene (the genetic cause) from his mother. The dystrophin gene is the largest gene found in nature and was identified through a positional cloning approach. It's a highly complex gene, a large rod-like cytoskeletal protein which is found at the inner surface of muscle fibers. www.ncbi.nlm.nih.gov - http://www.ncbi.nlm.nih.gov/.
The American Cancer Society publishes current advances made in cancer research on their website. Many of the exciting discoveries about how best to treat the disease focus on the genetic aspects associated with certain types of cancer. In addition, treatments aimed at genetic solutions to cancer may be more effective and may cause fewer adverse side effects than traditional cancer treatments (American Can...