Comprehensive and efficient HBB mutation analysis for detection of beta-hemoglobinopathies in a pan-ethnic population

Current methods that assay hemoglobin beta-globin chain variants can have limited clinical sensitivity when applied techniques identify only a predefined panel of mutations. Even sequence-based assays may be limited depending on which gene regions are investigated. We sought to develop a clinically...

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Bibliographic Details
Published in:American journal of clinical pathology 2010-05, Vol.133 (5), p.700-707
Main Authors: Chan, Owen T M, Westover, Kenneth D, Dietz, Lisa, Zehnder, James L, Schrijver, Iris
Format: Article
Language:English
Subjects:
beta-Globins - genetics
beta-Thalassemia - diagnosis
beta-Thalassemia - ethnology
beta-Thalassemia - genetics
California - epidemiology
Cultural Diversity
DNA Mutational Analysis - methods
Ethnic Groups
Gene Deletion
Genomics
Genotype
Hemoglobins - genetics
Humans
Mutation
Polymorphism, Genetic
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Summary:Current methods that assay hemoglobin beta-globin chain variants can have limited clinical sensitivity when applied techniques identify only a predefined panel of mutations. Even sequence-based assays may be limited depending on which gene regions are investigated. We sought to develop a clinically practical yet inclusive molecular assay to identify beta-globin mutations in multicultural populations. We highlight the beta-globin mutation detection assay (beta-GMDA), an extensive gene sequencing assay. The polymerase chain reaction (PCR) primers are located to encompass virtually all hemoglobin beta locus (HBB) mutations. In addition, this assay is able to detect, by gap PCR, a common large deletion (Delta619 base pair), which would be missed by sequencing alone. We describe our 5-year experience with the beta-GMDA and indicate its capability for detecting homozygous, heterozygous, and compound heterozygous sequence changes, including previously unknown HBB variants. The beta-GMDA offers superior sensitivity and ease of use with comprehensive detection of HBB mutations that result in beta-globin chain variants.
ISSN:0002-9173
1943-7722
DOI:10.1309/AJCP7HQ2KWGHECIO