Faculty Collaboration Database

VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population. Blood 2012 Mar 01;119(9):2135-40

Date

12/27/2011

Pubmed ID

22197721

Pubmed Central ID

PMC3311248

DOI

10.1182/blood-2011-10-384610

Scopus ID

2-s2.0-84857720362 (requires institutional sign-in at Scopus site)   91 Citations

Abstract

Diagnosis and classification of VWD is aided by molecular analysis of the VWF gene. Because VWF polymorphisms have not been fully characterized, we performed VWF laboratory testing and gene sequencing of 184 healthy controls with a negative bleeding history. The controls included 66 (35.9%) African Americans (AAs). We identified 21 new sequence variations, 13 (62%) of which occurred exclusively in AAs and 2 (G967D, T2666M) that were found in 10%-15% of the AA samples, suggesting they are polymorphisms. We identified 14 sequence variations reported previously as VWF mutations, the majority of which were type 1 mutations. These controls had VWF Ag levels within the normal range, suggesting that these sequence variations might not always reduce plasma VWF levels. Eleven mutations were found in AAs, and the frequency of M740I, H817Q, and R2185Q was 15%-18%. Ten AA controls had the 2N mutation H817Q; 1 was homozygous. The average factor VIII level in this group was 99 IU/dL, suggesting that this variation may confer little or no clinical symptoms. This study emphasizes the importance of sequencing healthy controls to understand ethnic-specific sequence variations so that asymptomatic sequence variations are not misidentified as mutations in other ethnic or racial groups.

Author List

Bellissimo DB, Christopherson PA, Flood VH, Gill JC, Friedman KD, Haberichter SL, Shapiro AD, Abshire TC, Leissinger C, Hoots WK, Lusher JM, Ragni MV, Montgomery RR

Authors

Thomas Abshire MD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin
Veronica H. Flood MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Kenneth D. Friedman MD Professor in the Medicine department at Medical College of Wisconsin
Robert R. Montgomery MD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Substitution
Exons
Gene Order
Genetic Variation
Humans
Mutation
von Willebrand Diseases
von Willebrand Factor