Novel missense mutation c.2685G>C (p.Q895H) in gene associated with very low levels of VWF mRNA

• Published in: Annals of hematology Vol. 88; no. 3; pp. 245 - 247
• Main Authors: Cabrera, Noelia, Casaña, Pilar, Cid, Ana Rosa, Haya, Saturnino, Moret, Andrés, Aznar, Jose Antonio
• Format: Journal Article
• Language: English
• Published: Springer Verlag 20.08.2008
• Subjects: Missense mutation; gene; von Willebrand disease; Low expression; Type 2N; Factor VIII binding capacity
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-008-0576-7

Homozygous patients for null alleles in gene show a severe von Willebrand phenotype, whereas compound heterozygous patients only show the phenotype of the expressed allele. Five members of the same family were studied. The two patients showed borderline VWF levels, a mild factor VIII (FVIII) deficiency and a decrease of the binding of VWF to exogenous FVIII. The genetic analyses of the gene confirmed that the patients were compound heterozygous for c.2561G>A (R854Q) and c.2685G>C (p.Q895H) mutations. The latter, is located in the 3′ extreme of exon 20, and it has not been previously described. Studies of the cDNA from platelet mRNA were performed to investigate the expression of p.H895 allele. The loss of heterozygosity at the cDNA level suggests a lack of expression of the p.H895 allele. The overall studies can explain the type 2N phenotype of the two patients, since the allele carrying the new missense mutation p.Q895H has shown a low expression of gene.