Journal article
F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity
Haemophilia : the official journal of the World Federation of Hemophilia, Vol.18(3), pp.375-382
Accepted after revision 23 October 2011
05/2012
DOI: 10.1111/j.1365-2516.2011.02700.x
PMID: 22103590
Abstract
Summary. Both genetic and treatment-related risk factors contribute to the development of inhibitors in haemophilia. An inhibitor surveillance system piloted at 12 US sites has the goal of assessing risk factors through prospective data collection. This report examines the relationship of genotype and race/ethnicity to history of inhibitor in a large cohort of US haemophilia patients. Mutation analysis was performed on 676 haemophilia A (HA) and 153 haemophilia B (HB) patients by sequencing, Multiplex Ligation-dependent Probe Amplification, and PCR for inversions in F8 introns 22 (inv22) and 1 (inv1). Two HB patients with deletions had history of inhibitor. In severe HA, frequency of history of inhibitor was: large deletion 57.1%, splice site 35.7%, inv22 26.8%, nonsense 24.5%, frameshift 12.9%, inv1 11.1% and missense 9.5%. In HA, 19.6% of 321 White non-Hispanics (Whites), 37.1% of 35 Black non-Hispanics (Blacks) and 46.9% of 32 Hispanics had history of inhibitor (P = 0.0003). Mutation types and novel mutation rates were similar across ethnicities. When F8 haplotypes were constructed, Whites and Hispanics showed only H1 and H2. Within H1, history of inhibitor was 12.4% in Whites, 40.0% in Blacks (P = 0.009) and 32.4% in Hispanics (P = 0.002). Inhibitor frequency is confirmed to vary by mutation type and race in a large US population. White patients with history of inhibitor did not exhibit rare F8 haplotypes. F8 gene analysis did not reveal a cause for the higher inhibitor frequencies in Black and Hispanic patients.
Details
- Title: Subtitle
- F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity
- Creators
- C. H MILLER - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAJ BENSON - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAD ELLINGSEN - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAJ DRIGGERS - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAA PAYNE - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAF. M KELLY - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAJ. M SOUCIE - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAW Craig Hooper - Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USAHemophilia Inhibitor Research Study Investigators
- Contributors
- Steven R Lentz (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Haemophilia : the official journal of the World Federation of Hemophilia, Vol.18(3), pp.375-382
- Edition
- Accepted after revision 23 October 2011
- Publisher
- Blackwell Publishing Ltd
- DOI
- 10.1111/j.1365-2516.2011.02700.x
- PMID
- 22103590
- ISSN
- 1351-8216
- eISSN
- 1365-2516
- Number of pages
- 8
- Language
- English
- Date published
- 05/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094553002771
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