Novel missense mutation c.2685G>C (p.Q895H) in VWF gene associated with very low levels of VWF mRNA.
Homozygous patients for null alleles in VWF 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 VWF 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 VWF gene.
Cabrera
Noelia
N
Unidad de Coagulopatías Congénitas, Hospital Universitario La Fe., Av. Campanar 21, 46009 Valencia, Spain.
Casaña
Pilar
P
Cid
Ana Rosa
AR
Haya
Saturnino
S
Moret
Andrés
A
Aznar
Jose Antonio
JA
D000483:Alleles; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics*; D014842:von Willebrand Diseases / Q000175:diagnosis / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics*
D012333:RNA, Messenger; D014841:von Willebrand Factor