Linked Life Data

9323559

Source:http://linkedlifedata.com/resource/pubmed/id/9323559

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-11-6
pubmed:abstractText
Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the lysosomal exoglycosidase responsible for the hydrolysis of terminal alpha-galactosyl residues from glycoconjugates and is the defective enzyme causing Fabry disease (McKusick 301500). An unusally elevated level of plasma alpha-Gal A activity (> 2.5 times the normal mean) was detected in two unrelated normal males and the elevated activities were inherited as X-linked traits in their families. Sequencing of the alpha-Gal A coding region, intron/exon boundaries and 5'-flanking region from the proband identified a single mutation, a G-->A transition 30 nt upstream from the initiation of translation codon in exon 1. The -30G-->A mutation occurred in a putative NF kappa B/Ets consensus binding site that was recently shown to inhibit protein binding to the 5'-untranslated region of the gene, providing a possible explanation for its high activity. To further characterize the mutation, the mRNA and protein expressed by this variant allele were studied. Purified plasma and lymphoblast alpha-Gal A activity from individuals with the -30G-->A mutation had normal physical and kinetic properties. In vitro translation of mRNAs from the cloned normal and high plasma activity alleles resulted in similar levels of alpha-Gal A protein, indicating that this mutation did not enhance translation. These findings suggest that the -30G-->A mutation in the 5'-untranslated region of the alpha-Gal A gene enhances transcription, presumably by interfering with the binding of negatively-acting transcription factors which normally decrease alpha-Gal A expression in various cells. Preliminary studies of the frequency of the -30G-->A mutation in 395 unrelated normal males of mixed ancestry revealed two additional unrelated individuals who had high plasma enzymatic activity and the mutation, confirming the effect of this mutation on enzyme expression and suggesting that about 0.5% of normal individuals have high plasma alpha-Gal A activity due to this variant allele.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0141-8955
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
643-57
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Human alpha-galactosidase A: high plasma activity expressed by the -30G-->A allele.
pubmed:affiliation
Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.