title: Characterization of the HBB: c.*233G > C Variant: No Evidence of a β-Thalassemic Phenotype.
abstract: β-Thalassemia (β-thal) results from homozygous or compound heterozygous inheritance of β-globin alleles that yield decreased or absent synthesis of the β chain. Disease is frequently severe, requiring lifelong transfusion therapy. Heterozygosity for a β-thal allele results in an asymptomatic carrier state with mild but characteristic hematological findings. More than 200 β-globin alleles have been demonstrated to produce β-thal. For populations with a high prevalence of β-thal, screening for carrier status, genetic counseling and prenatal diagnosis are important components of efforts to both reduce disease incidence and provide early diagnosis and treatment. It is therefore important to define and characterize potential β-thal alleles. We sought to further characterize the previously reported β-thal allele, HBB: c.*233G > C. This variant is provisionally included in the HbVar database based on a study of Palestinians in the Gaza Strip with β-thal disease or carrier status (known or suspected) where 4.2% of subjects were found to have HBB: c.*233G > C. In our patient population, we detected the HBB: c.*233G > C variant in 17.3% of individuals (17 heterozygotes, one homozygote) undergoing β hemoglobin (Hb) gene sequencing at our laboratory over a 25-month period. Hematological parameters were analyzed to determine if these individuals demonstrated findings consistent with inheritance of a β-thal allele. Individuals with the HBB: c.*233G > C variant did not demonstrate any abnormalities in hematological parameters characteristic of β-thal carrier state (17 heterozygotes) or clinical evidence of disease (homozygote). Our data demonstrate no evidence for pathogenicity of the HBB: c.*233G > C variant but rather demonstrate that this variant is a common benign polymorphism.
authors.affiliation: a Bloodworks Northwest , Seattle , Washington , USA.|b Department of Pathology , University of Texas Southwestern Medical Center , Dallas , Texas , USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: c Department of Pathology , Children's Health , Dallas , Texas , USA.
authors.forename: Midori
authors.initials: M
authors.lastname: Mitui
authors.affiliation: c Department of Pathology , Children's Health , Dallas , Texas , USA.|d Department of Pathology and the Eugene McDermott Center for Human Growth and Development , University of Texas Southwestern Medical Center , Dallas , Texas , USA.
authors.forename: Jason Y
authors.initials: JY
authors.lastname: Park
authors.affiliation: b Department of Pathology , University of Texas Southwestern Medical Center , Dallas , Texas , USA.|c Department of Pathology , Children's Health , Dallas , Texas , USA.
authors.forename: Hung S
authors.initials: HS
authors.lastname: Luu
authors.affiliation: b Department of Pathology , University of Texas Southwestern Medical Center , Dallas , Texas , USA.|c Department of Pathology , Children's Health , Dallas , Texas , USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Timmons
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D055544:beta-Globins
keywords: HBB: c.*233G > C; polymorphism; rs12788013; β-Thalassemia (β-thal)