RESUMO
Hemoglobin (Hb) variants are abnormalities resulting from point mutations in either of the two α-globin genes (HBA2 or HBA1) or the ß-globin gene (HBB). Various reports of Hb variants have been described in Iran and other countries around the world. Hb Setif (or HBA2: c.283G>T) is one of these variants with a mutation at codon 94 of of the α2-globin gene that is characterized in clinically normal heterozygous individuals. We here report clinical and hematological findings in two homozygous cases of Iranian origin for this unstable Hb variant.
Assuntos
Hemoglobinas Anormais/genética , Mutação Puntual , alfa-Globinas/genética , Adulto , Heterozigoto , Humanos , Irã (Geográfico)RESUMO
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.
Assuntos
Anemia Hipocrômica/genética , Hemoglobinas Glicadas/genética , Mutação , Sítios de Splice de RNA , Talassemia alfa/genética , Adulto , Sequência de Bases , Feminino , Genes Dominantes , Humanos , Masculino , Dados de Sequência Molecular , alfa-Globinas/genéticaRESUMO
In the present study, a total of 11 individuals with hypochromic microcytic anemia who did not reveal the most common α-thalassemia (α-thal) deletions or mutations, were subjected to more investigations by DNA sequencing of the α-globin genes. Seven novel nondeletional α-thal mutations localized on the α2-globin gene in the heterozygous state were identified. These mutations either corrupted regulatory splice sites and consequently affected RNA processing or created unstable hemoglobin (Hb) variants. The mutations described here produced globin gene variants that lead to amino acid changes in critical regions of the globin chain. The clinical presentation of most patients was a persistent mild microcytic anemia similar to an α(+)-thal. In the last decade, numerous α-globin mutations have been observed leading to an α-thal phenotype and these studies have been considered to be important as discussed here.
Assuntos
Mutação , alfa-Globinas/genética , Talassemia alfa/genética , Adolescente , Adulto , Alelos , Criança , Biologia Computacional/métodos , Índices de Eritrócitos , Éxons , Feminino , Ordem dos Genes , Loci Gênicos , Heterozigoto , Humanos , Masculino , Fenótipo , Deleção de Sequência , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/diagnósticoRESUMO
We describe a case of Hb H disease associated with homozygosity for a two nucleotide deletion in the polyadenylation signal of the α2-globin gene (HBA2: c.*93_*94delAA). The patient, a 27-year-old son of a consanguineous couple, needs regular blood transfusions every 6 months.
