Compound heterozygosity for two novel mutations (1203insG/Y1456X) in the von Willebrand factor gene causing type 3 von Willebrand disease.
A 23-year-old Chinese woman with severe von Willebrand factor (VWF) deficiency and her parents were investigated by PCR/direct sequencing of the VWF gene. The patient was found to be compound heterozygous for two novel null mutations. The first was a microinsertion in exon 8 (1203insG) that introduced a frameshift at codon 298 leading to premature translational termination at codon 302. The second was a C to A transversion in exon 28 which resulted in the replacement of tyrosine 562 by a stop codon (Y1456X). The failure to amplify VWF cDNA from the patient by semi-nested PCR is consistent with the induction of nonsense-mediated mRNA decay.
Xie
F
F
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China. topxiefei@126.com
Wang
X
X
Cooper
D N
DN
Lan
F
F
Fang
Y
Y
Cai
X
X
Wang
Z
Z
Wang
H
H
D000328:Adult; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics*
D018076:DNA, Complementary; D014841:von Willebrand Factor