title: Identification of Mutations Causing Aberrant Termination and Deficient Splice Donor Site on the HBA1 Gene.
abstract: α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects on the α-globin gene cluster can result in α-thal that may develop a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. In the present study, four Iranian individuals with hypochromic microcytic anemia, who revealed none of the known mutations responsible for α-thal, were subjected for further investigations. The thalassemic phenotype of these patients resulted from abnormal RNA splicing sites owing to a missense at the splice donor site, a truncated protein or hemoglobin (Hb) variants as a result of two different substitutions on the α1-globin gene. The clinical presentation of mild anemia in these individuals showed the contribution of these novel mutations in α-thal in spite of the dominantly expressed α2-globin gene. This study describes hematological manifestations of subjects carrying some novel mutations comparable to the reported phenotype of α(+)-thal trait.
authors.affiliation: a Genetics Research Centre , University of Social Welfare & Rehabilitation Sciences , Tehran , Iran.|b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Farashi
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Shadi
authors.initials: S
authors.lastname: Vakili
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Negin F
authors.initials: NF
authors.lastname: Garous
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Mehri
authors.initials: M
authors.lastname: Ashki
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Forouzesh Pour
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Zeinali
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Rad
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Hashem
authors.initials: H
authors.lastname: Imanian
authors.affiliation: b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.|c Iranian Blood Transfusion Organization , High Institute for Transfusion Research Centre , Tehran , Iran.
authors.forename: Azita
authors.initials: A
authors.lastname: Azarkeivan
authors.affiliation: a Genetics Research Centre , University of Social Welfare & Rehabilitation Sciences , Tehran , Iran.|b Department of Molecular Genetics , Kariminejad-Najmabadi Pathology & Genetics Centre , Tehran , Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
mesh_terms: D000328:Adult; D000747:Anemia, Hypochromic / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D005799:Genes, Dominant; D006442:Glycated Hemoglobin / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D022821:RNA Splice Sites; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D006442:Glycated Hemoglobin; D022821:RNA Splice Sites; D055542:alpha-Globins
keywords: RNA splicing sites; hypochromic microcytic anemia; truncated protein; α-Thalassemia (α-thal)