Single Point Mutation in Human Glycoprotein IIIa Is Associated With a New Platelet-Specific Alloantigen (Mo) Involved in Neonatal Alloimmune Thrombocytopenia

Here we describe a new platelet-specific alloantigen that was identified in a case of neonatal alloimmune thrombocytopenia. This antigen has provisionally been called “Mo.” By studying the Mo family, it was shown to be inherited in an autosomal dominant manner. Immunoprecipitation and Western blot a...

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Bibliographic Details
Published in:	Blood Vol. 81; no. 1; pp. 70 - 76
Main Authors:	Kuijpers, R.W.A.M., Simsek, S., Faber, N.M., Goldschmeding, R., Wermerkerken, R.K.V. van, Borne, A.E.G. Kr. von dem
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 01-01-1993 The Americain Society of Hematology
Subjects:	Base Composition Base Sequence Biological and medical sciences Blood Platelets - immunology Blotting, Western DNA - genetics Hematologic and hematopoietic diseases Humans Immunosorbent Techniques Infant, Newborn Isoantigens - genetics Isoantigens - immunology Male Medical sciences Molecular Sequence Data Nucleic Acid Hybridization Oligonucleotide Probes - chemistry Pedigree Platelet diseases and coagulopathies Platelet Membrane Glycoproteins - genetics Platelet Membrane Glycoproteins - immunology Point Mutation Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Thrombocytopenia - genetics Thrombocytopenia - immunology Human Thrombocytopenia Platelet Alloantigen Newborn Point mutation Hemopathy Mutation Alloimmunization
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Summary:	Here we describe a new platelet-specific alloantigen that was identified in a case of neonatal alloimmune thrombocytopenia. This antigen has provisionally been called “Mo.” By studying the Mo family, it was shown to be inherited in an autosomal dominant manner. Immunoprecipitation and Western blot analysis showed that the antigen resides on platelet glycoprotein IIIa (GP IIIa). Genomic analysis, performed by applying polymerase chain reaction and sequencing, showed a C → G substitution of base pair 1267 of the coding region of the DNA for GP IIIa, resulting in a substitution of Proline407 by Alanine407. That this substitution is associated with the antigen could be demonstrated by restriction fragment length polymorphism analysis of cDNA, prepared from platelet RNA, and of genomic DNA. It was confirmed by dot-blot hybridization with allele-specific oligonucleotides. All family members, also those being Mo antigen-positive, were healthy. None of them appeared to suffer from increased tendency of bleeding or thrombosis. Thus, the Mo mutation does not lead to significant platelet dysfunction in vivo with heterozygous carriers. One of 450 random healthy blood donors who were tested was positive for the Mo antigen. Typing was performed by the classical serologic methods as well as by DNA analysis.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood.V81.1.70.70