Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Canine leukocyte adhesion deficiency (CLAD) is a fatal immunodeficiency disease found in Irish setters. The clinical manifestations of CLAD are very similar to LAD in humans and BLAD in cattle, which are both caused by mutations in ITGB2 encoding the leukocyte integrin beta-2 subunit (CD18). Sequence analysis of the ITGB2 coding sequence from a CLAD dog and a healthy control revealed a single missense mutation, Cys36Ser. This cysteine residue is conserved among all beta integrins, and the mutation most likely disrupts a disulfide bond. The mutation showed a complete association with CLAD in Irish setters and was not found in a sample of dogs from other breeds. The causative nature of this mutation was confirmed by transduction experiments using retroviral vectors and human LAD EBV B-cells. The normal canine CD18 formed heterodimers with the human CD11 subunit, whereas gene transfer of the mutant CD18 resulted in very low levels of CD11/CD18 expression. The identification of the causative mutation for CLAD now makes it possible to identify carrier animals with a simple diagnostic DNA test, and it forms the basis for using CLAD as a large animal model for the development and evaluation of clinical treatments for human LAD.
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PMID:A missense mutation in the beta-2 integrin gene (ITGB2) causes canine leukocyte adhesion deficiency. 1051 85

Leukocyte adhesion deficiency type-1(LAD-1) is one of the immunodeficiency autosomal recessive diseases that results from mutation in integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) ITGB2 gene. The aim of this study was to investigate molecular prenatal diagnosis of LAD-1. Four pregnant women with five fetuses (one pregnancy was twin) with clinical and laboratory diagnosis of LAD-1 in their previous children were studied. The chorionic villus sampling (CVS) was obtained when mothers were in 10-12th weeks of gestation. Mutation analysis of ITGB2 gene for affected children revealed 3 misssense mutations (c.382G>A, a novel mutation, c.2146G>C, and c.715G>A) and one splice site novel mutation (c.1877+2G>A). All of Parents were heterozygous for these mutations. Consideration of affected gene regions for five CVS samples showed two homozygotes and one heterozygote for mutant allele and two homozygotes for normal allele. Interestingly, one of the twin fetuses was affected and another was normal. Briefly, two cases of CVS samples were affected and three cases of remained CVS samples were unaffected.This is the first report of prenatal diagnosis of LAD-1 from Iran with two new mutations that can be used for genetic and prenatal diagnosis for all patients suspected to LAD1 and can be helpful to prevent the birth of affected children with LAD-1. This abstract presented in the second international congress of Immunology, Asthma and Allergy, Tehran, Iran 2013.
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PMID:Prenatal diagnosis of leukocyte adhesion deficiency type-1 (five cases from iran with two new mutations). 2433 30