New mutation in the platelet beta3-integrin gene: implication for the diagnosis of fetomaternal alloimmunization.

Background: Fetal ventriculomegaly is a relatively common finding and fetomaternal alloimmune thrombocytopenia may be one of the causes.

Study Design And Methods: Such a case discovered at 21 weeks of gestation leading to platelet (PLT) immunologic testing is reported here. PLT genotyping was performed by polymerase chain reaction (PCR)-sequence-specific primers (SSPs) method and PCR-restriction fragment length polymorphism (RFLP) analysis. Serologic investigation was done with the monoclonal antibody-specific immobilization of PLT antigens technique.

Results: The mother was found to be HPA-1b homozygous and the father HPA-1a homozygous with PCR-SSP, but the mother was found to be HPA-1 heterozygous by phenotyping. This result was confirmed by PCR-RFLP. Sequencing of the glycoprotein IIIa exon 3 revealed a heterozygous mutation 262T > C, which does not induce an amino acid change. It is localized in the sequence of the antisense primer of the HPA-1 PCR-SSP, inducing the sole amplification of the DNA copy bearing the HPA-1b allele.

Conclusion: Even if such mutations are a rare event, PLT phenotyping is still of interest to avoid rare false PLT typing assignation, the unknown polymorphism being only discovered by such a combination of techniques.