Mutation spectra of the ITGB2 gene in Iranian families with Leukocyte Adhesion Deficiency type 1

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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.

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