Genetics of type 1 von Willebrand disease

Current Opinion in Hematology

Volumn 14, Issue 5, 2007, Pages 444-449

  Goodeve, Anne ^a,b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b UNIVERSITY OF SHEFFIELD   (United Kingdom)

Author keywords

Genetic analysis; Mutation; Von Willebrand disease; Von Willebrand factor

Indexed keywords

VON WILLEBRAND FACTOR;

AMINO ACID SEQUENCE; BLOOD GROUP O; GENE MUTATION; GENETIC ASSOCIATION; HUMAN; LINKAGE ANALYSIS; MISSENSE MUTATION; POPULATION; PREVALENCE; PRIORITY JOURNAL; PROTEIN GLYCOSYLATION; REVIEW; VON WILLEBRAND DISEASE;

ABO BLOOD-GROUP SYSTEM; ANIMALS; HUMANS; LINKAGE (GENETICS); MUTATION, MISSENSE; PREVALENCE; PROMOTER REGIONS (GENETICS); RISK FACTORS; RNA SPLICE SITES; VON WILLEBRAND DISEASE; VON WILLEBRAND FACTOR;

EID: 34648819054     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e32826f4b41     Document Type: Review

References (35)

1. Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 1987; 69:454-459.
2. Werner EJ, Broxson EH, Tucker EL, et al. Prevalence of von Willebrand disease in children: a multiethnic study. J Pediatr 1993; 123:893-898.
3. Bloom AL. von Willebrand factor: clinical features of inherited and acquired disorders. Mayo Clin Proc 1991; 66:743-751.
4. Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 1994; 71:520-525.
5. Sadler JE, Budde U, Eikenboom JC, et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4:2103-2114. This is an update of the VWD classification from the ISTH-SSC on VWF. Notably, the classification of type 1 has been relaxed since the 1994 classification [4] to include further variants that may have abnormal VWF subunits but have normal activity in relation to plasma antigen levels and in which the proportion of large multimers is not significantly decreased, but may have minor structural abnormalities.
6. ••]. Although it at first appears that VWF is not important in VWD in the majority of families in these studies, this figure does not include, among others, involvement of the gene in families with incompletely penetrant mutations, or families more than one independently inherited mutation.
7. ••], this provides a first insight into mutation spectrum in sizeable cohorts of patients with type 1 VWD.
8. ••]. The paper includes an estimate of the contribution of the VWF gene to low VWF plasma level.
9. ••], demonstrated the wide range of different mutations resulting in type 1, the large number of patients lacking a mutation and the extent to which bleeding symptoms were similar in groups of patients with or without a VWF mutation.
10. Cumming A, Grundy P, Keeney S, et al. An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease. Thromb Haemost 2006; 96:630-641. Report on a mutation and linkage analysis in 32 UK families with type 1 VWD demonstrating candidate mutations in 53%. R1205H (13%) and Y1584C (25%) were both commonly seen in the index cases and family members, with Y1584C being associated with ABO blood group O in 95% of patients.
11. Lanke E, Johansson AM, Hallden C, Lethagen S. Genetic analysis of 31 Swedish type 1 von Willebrand disease families reveals incomplete linkage to the von Willebrand factor gene and a high frequency of a certain disease haplotype. J Thromb Haemost 2005; 3:2656-2663.
12. Castaman G, Eikenboom JC, Bertina RM, Rodeghiero F. Inconsistency of association between type 1 von Willebrand disease phenotype and genotype in families identified in an epidemiological investigation. Thromb Haemost 1999; 82:1065-1070.
13. Casana P, Martinez F, Haya S, et al. Significant linkage and nonlinkage of type 1 von Willebrand disease to the von Willebrand factor gene. Br J Haematol 2001; 115:692-700.
14. O'Brien LA, James PD, Othman M, et al. Founder von Willebrand factor haplotype associated with type 1 von Willebrand disease. Blood 2003; 102:549-557.
15. Sodetz JM, Paulson JC, McKee PA. Carbohydrate composition and identi-fication of blood group A, B, and H oligosaccharide structures on human Factor VIII/von Willebrand factor. J Biol Chem 1979; 254:10754-10760.
16. Matsui T, Titani K, Mizuochi T. Structures of the asparagine-linked oligosaccharide chains of human von Willebrand factor. Occurrence of blood group A, B, and H(O) structures. J Biol Chem 1992; 267:8723-8731.
17. Gill JC, Endres-Brooks J, Bauer PJ, et al. The effect of ABO blood group on the diagnosis of von Willebrand Disease. Blood 1987; 69:1691-1695.
18. Donner M, Kristoffersson AC, Berntorp E, et al. Two new candidate mutations in type IIA von Willebrand's disease (Arg834->Gly, Gly846->Arg) and one polymorphism (Tyr821->Cys) in the A2 region of the von Willebrand factor. Eur J Haematol 1993; 51:38-44.
19. Bowen DJ. An influence of ABO blood group on the rate of proteolysis of von Willebrand factor by ADAMTS13. J Thromb Haemost 2003; 1:33-40.
20. Bowen DJ, Collins PW. Insights into von Willebrand factor proteolysis: clinical implications. Br J Haematol 2006; 133:457-467. This review presents a current understanding of VWF proteolysis by ADAMTS13, the VWF-cleaving protease, and a model of how this may be relevant to type 1 VWD.
21. Davies JA, Collins PW, Hathaway LS, Bowen DJ. The effect of von Willebrand factor Y/C1584 on in vivo protein level and function, and interaction with ABO blood group. Blood 2007; 109:2840-2846. Investigation of the effect of blood group O and Y1584C, common factors contributing to type 1 VWD. The paper demonstrates that the combined factors act synergistically to reduce VWF level and impair its function.
22. van Schooten CJ, Denis CV, Lisman T, et al. Variations in glycosylation of von Willebrand factor with O-linked sialylated T antigen are associated with its plasma levels. Blood 2007; 109:2430-2437. This paper suggests a potential association between O-linked glycosylation and VWF survival. Much work has previously focused on N-linked ABO glycosylation; this work may highlight a further aspect of modulation of VWF levels through potential differences in O-linked glycosylation.
23. Mohlke KL, Purkayastha AA, Westrick RJ, et al. Mvwf, a dominant modifier of murine von Willebrand factor, results from altered lineage-specific expression of a glycosyltransferase. Cell 1999; 96:111-120.
24. Lemmerhirt HL, Shavit JA, Levy GG, et al. Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine VWF gene. Blood 2006; 108:3061-3067. This paper reports on a murine gain-of-function mutation resulting from R2657Q in VWF, leading to raised plasma VWF level, which suggests that similar human variants may contribute to variation in VWF levels in humans.
25. Lemmerhirt HL, Broman KW, Shavit JA, Ginsburg D. Genetic regulation of plasma von Willebrand factor levels: quantitative trait loci analysis in a mouse model. J Thromb Haemost 2007; 5:329-335. This paper reports on genetic linkage of VWF level to two additional loci in mice that may also have relevance in humans once the genes responsible are identified.
26. Lenting PJ, Westein E, Terraube V, et al. An experimental model to study the in vivo survival of von Willebrand factor. Basic aspects and application to the R1205H mutation. J Biol Chem 2004; 279:12102-12109.
27. van Schooten CJ, Tjernberg P, Westein E, et al. Cysteine-mutations in von Willebrand factor associated with increased clearance. J Thromb Haemost 2005; 3:2228-2237.
28. Haberichter SL, Balistreri M, Christopherson P, et al. Assay of the von Willebrand factor (VWF) propeptide to identify patients with type 1 von Willebrand disease with decreased VWF survival. Blood 2006; 108:3344-3351. Decreased survival of VWF infamilies with type 1 VWD was illustrated by use of assays for the VWF propeptide and for VWF:Ag. The combined assays could be a simple means of seeking patients with reduced survival phenotype. The authors suggest that the patients are classified as having clearance mutations (type 1C VWD).
29. Eikenboom JC, Matsushita T, Reitsma PH, et al. Dominant type 1 von Willebrand disease caused by mutated cysteine residues in the D3 domain of von Willebrand factor. Blood 1996; 88:2433-2441.
30. Casana P, Cabrera N, Haya S, et al. Von Willebrand's disease: a novel mutation, P1824H and the incidence of R1205H defect among families with dominant quantitative von Willebrand factor deficiency. Haematologica 2006; 91:1130-1133. This short report details mutation analysis in seven families with dominantly inherited type 1 VWD, and illustrates the prevalence of R1205H in this disorder, identified in five of the families.
31. Lester WA, Guilliatt AM, Surdhar GK, et al. Inherited and de novo von Willebrand disease 'Vicenza' in UK families with the R1205H mutation: diagnostic pitfalls and new insights. Br J Haematol 2006; 135:91-96. R1205H was shown to be the most commonly identified mutation in dominantly inherited type 1 VWD in a single UK centre. Very low plasma VWF levels, but a less severe clinical phenotype, which are characteristic of this mutation, were observed.
32. Casonato A, Pontara E, Sartorello F, et al. Identifying type Vicenza von Willebrand disease. J Lab Clin Med 2006; 147:96-102. Analysis of plasma and platelet VWF levels was used to identify individuals with Vicenza type VWD, resulting from the R1205H mutation
33. •].
34. ••].
35. James P, Lillicrap D. Genetic testing for von Willebrand disease: the Canadian experience. Semin Thromb Hemost 2006; 32:546-552. This review summarizes the Canadian perspective on utility of mutation analysis in VWD. It nicely summarizes the current situation in type 1 VWD by stating that we do not yet understand enough about the significance of many identified VWF sequence alterations to start seeking them diagnostically.