Q1311X: a novel nonsense mutation of putative ancient origin in the von Willebrand factor gene.
Type 3 von Willebrand disease, a recessive autosomally inherited bleeding disorder, refers to complete deficiency of von Willebrand factor (VWF). The novel Q1311X mutation was detected in the homozygous state in four Spanish patients from two apparently unrelated families of gypsy origin. The lack of specific amplification of platelet VWF cDNA from two of the patients indicates reduced levels of mutated gene expression. The similar haplotype linked to mutated alleles suggests a common origin. On the basis of the two instabilities observed and the estimated mutation rate of the microsatellites of intron 40 of the VWF gene, we can estimate that this mutation could have arisen about 2300 years ago.
Casaña
P
P
Unidad de Coagulopatías Congénitas de la Comunidad Valenciana, and Unidad de Genética y Diagnóstico Prenatal, Hospital Universitari La Fe, Valencia, Spain. casanya_pil@gva.es
Martínez
F
F
Haya
S
S
Lorenzo
J I
JI
Espinós
C
C
Aznar
J A
JA
D018389:Codon, Nonsense / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006178:Romani People; D013030:Spain; D014842:von Willebrand Diseases / Q000235:genetics*; D014841:von Willebrand Factor / Q000235:genetics*
D018389:Codon, Nonsense; D014841:von Willebrand Factor