Linked Life Data

11418466

Source:http://linkedlifedata.com/resource/pubmed/id/11418466

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-6-21
pubmed:abstractText
A new mutation is described in the X-linked gene GATA1, resulting in macrothrombocytopenia and mild dyserythropoietic features but no marked anemia in a 4-generation family. The molecular basis for the observed phenotype is a substitution of glycine for aspartate in the strictly conserved codon 218 (D218G) of the amino-terminal zinc finger loop of the transcription factor GATA1. Zinc finger interaction studies demonstrated that this mutation results in a weak loss of affinity of GATA1 for its essential cofactor FOG1, whereas direct D218G-GATA1 binding to DNA was normal. The phenotypic effects of this mutation in the patients' platelets have been studied. Semiquantitative RNA analysis, normalized for beta-actin messenger RNA, showed extremely low transcription of the GATA1 target genes GPIbbeta and GPIX but also a significantly lower expression of the nondirectly GATA1-regulated Gsalpha gene, suggestive of incomplete megakaryocyte maturation. In contrast, GPIIIa expression was close to normal in agreement with its early appearance during megakaryocyte differentiation. Flow cytometric analysis of patient platelets confirmed the existence of a platelet population with abnormal size distribution and reduced GPIb complex levels but with normal GPIIIa expression. It also showed the presence of very immature platelets lacking almost all membrane glycoproteins studied (GPIbalpha, GPIbbeta, GPIIIa, GPIX, and GPV). Patients' platelets showed weak ristocetin-induced agglutination, compatible with the disturbed GPIb complex. Accordingly, electron microscopy of the patients' platelets revealed giant platelets with cytoplasmic clusters consisting of smooth endoplasmic reticulum and abnormal membrane complexes. In conclusion, GATA1 mutations can lead to isolated X-linked macrothrombocytopenia without anemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-92
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11418466-Adult, pubmed-meshheading:11418466-Blood Platelets, pubmed-meshheading:11418466-Carrier Proteins, pubmed-meshheading:11418466-DNA Mutational Analysis, pubmed-meshheading:11418466-DNA-Binding Proteins, pubmed-meshheading:11418466-Erythrocytes, pubmed-meshheading:11418466-Erythroid-Specific DNA-Binding Factors, pubmed-meshheading:11418466-Family Health, pubmed-meshheading:11418466-Female, pubmed-meshheading:11418466-GATA1 Transcription Factor, pubmed-meshheading:11418466-Genetic Linkage, pubmed-meshheading:11418466-Haplotypes, pubmed-meshheading:11418466-Humans, pubmed-meshheading:11418466-Male, pubmed-meshheading:11418466-Mutation, pubmed-meshheading:11418466-Nuclear Proteins, pubmed-meshheading:11418466-Pedigree, pubmed-meshheading:11418466-Platelet Aggregation, pubmed-meshheading:11418466-Platelet Membrane Glycoproteins, pubmed-meshheading:11418466-Thrombocytopenia, pubmed-meshheading:11418466-Transcription Factors, pubmed-meshheading:11418466-X Chromosome, pubmed-meshheading:11418466-Zinc Fingers
pubmed:year
2001
pubmed:articleTitle
Platelet characteristics in patients with X-linked macrothrombocytopenia because of a novel GATA1 mutation.
pubmed:affiliation
Center for Molecular and Vascular Biology, Center for Human Genetics, Department of Pathology, University of Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't