Linked Life Data

7901025

Source:http://linkedlifedata.com/resource/pubmed/id/7901025

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1993-12-14
pubmed:databankReference
pubmed:abstractText
Leukocyte adhesion deficiency (LAD) is an autosomal recessive disease caused by heterogeneous mutations within the gene encoding the common beta subunit (CD18) of the three leukocyte integrins LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and p150,95 (CD11c/CD18). Based on the level of expression of CD18 on patient leukocytes, two phenotypes of LAD have been defined (severe and moderate) which correlate with the severity of the disease. We have investigated the molecular basis of the disease in two unrelated severe patients (HS and ZJO). Both patients share a complete absence of CD18 protein precursor and cell surface expression, but they differ in the level of CD18 mRNA, which is normal in HS and undetectable by Northern blot in ZJO. Determination of the primary structure of the patient HS CD18 mRNA revealed a 10-base pair deletion between nucleotides 190-200 (CD18 exon 3), which eliminates residues 41-43 and causes a frameshift into a premature termination codon 17 base pairs downstream from the deleted region. The 10-base pair frameshift deletion maps to a region of the CD18 gene where aberrant mRNA processing has been detected in HS and two other unrelated LAD patients. In the ZJO patient, amplification of lymphoblast CD18 mRNA demonstrated the presence of a non-sense mutation in the third nucleotide of the triplet encoding Cys534 (TGC-->TGA), within exon 12. Both genetic abnormalities were also detected at the genomic level, and affect the restriction pattern of their corresponding genes, thus enabling the detection of the mutant alleles among healthy heterozygous alleles in family studies. The identification of two new LAD CD18 alleles, either carrying a non-sense mutation (ZJO) or a partial gene deletion (HS), further illustrates the heterogeneity of the genetic alterations in LAD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:geneSymbol
CD18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2792-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Characterization of two new CD18 alleles causing severe leukocyte adhesion deficiency.
pubmed:affiliation
Unidad de Biología Molecular, Hospital de la Princesa, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Case Reports, Research Support, Non-U.S. Gov't