Novel homozygous mutation (c.175delG) in platelet glycoprotein ITGA2B gene as cause of Glanzmann's thrombasthenia type I.
BACKGROUND
Glanzmann's thrombasthenia (GT), is a rare autosomal recessive bleeding disorder. Platelets from patients with GT show quantitative or qualitative defects of the platelet membrane glycoprotein (GP) IIb/IIIa complex. A variety of genetic defects in ITGA2B and ITGB3 (genes for GPIIb and GPIIIa) has been described causing the clinical entity of GT.


METHODS
A newborn with bleeding symptoms (petechiae) platelet analyses revealed an inherited primary hemostasis disorder.


RESULTS
Analyses of patient's platelets using flow cytometry and immunoblotting showed absence of GPIIb protein and reduced amount of GPIIIa. Using restriction fragment length polymorphism heterozygosity for the deletion could be identified in the parents and in two siblings. Expression studies in mammalian cells revealed that the mutant GPIIb is missing and additionally affects the expression of wildtype GPIIIa. This deletion leads to a truncation at the very N-terminal region of the GPIIb protein.


CONCLUSIONS
The present study describes a patient with GT associated with a novel homozygous deletion (c.175delG) in exon 1 of ITGA2B. This deletion led to a reading frameshift and caused a severely truncated form of GPIIb.
Department of Pediatrics and Adolescent Medicine, University Hospital Freiburg, Germany.
C
C
Vannier
W
W
Behnisch
I
I
Bartsch
K
K
Sandrock
F
F
Ertle
K
K
Schmidt
A
A
Busse
A
A
Superti-Furga
A
A
Kulozik
S
S
Santoso
B
B
Zieger
D000483:Alleles; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation; D005808:Genes, Recessive / Q000235:genetics; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D010974:Platelet Aggregation / Q000235:genetics; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D013915:Thrombasthenia / Q000175:diagnosis / Q000235:genetics*
D019039:Platelet Glycoprotein GPIIb-IIIa Complex