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A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease.
Hemoglobin. 2015; 39(3):196-200.H

Abstract

α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered.

Authors+Show Affiliations

Kariminejad-Najmabadi Pathology & Genetics Center , Tehran , Iran .No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25976776

Citation

Farashi, Samaneh, et al. "A 21 Nucleotide Duplication On the Α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease." Hemoglobin, vol. 39, no. 3, 2015, pp. 196-200.
Farashi S, Faramarzi Garous N, Zeinali F, et al. A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease. Hemoglobin. 2015;39(3):196-200.
Farashi, S., Faramarzi Garous, N., Zeinali, F., Vakili, S., Ashki, M., Imanian, H., Najmabadi, H., Azarkeivan, A., & Tamaddoni, A. (2015). A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease. Hemoglobin, 39(3), 196-200. https://doi.org/10.3109/03630269.2015.1030757
Farashi S, et al. A 21 Nucleotide Duplication On the Α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease. Hemoglobin. 2015;39(3):196-200. PubMed PMID: 25976776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease. AU - Farashi,Samaneh, AU - Faramarzi Garous,Negin, AU - Zeinali,Fatemeh, AU - Vakili,Shadi, AU - Ashki,Mehri, AU - Imanian,Hashem, AU - Najmabadi,Hossein, AU - Azarkeivan,Azita, AU - Tamaddoni,Ahmad, Y1 - 2015/05/15/ PY - 2015/5/16/entrez PY - 2015/5/16/pubmed PY - 2016/3/25/medline KW - 21 nucleotide (nt) duplication KW - Hb H disease KW - Iran KW - α-Thalassemia (α-thal) KW - – –MED double α-globin gene deletion SP - 196 EP - 200 JF - Hemoglobin JO - Hemoglobin VL - 39 IS - 3 N2 - α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered. SN - 1532-432X UR - https://www.unboundmedicine.com/medline/citation/25976776/A_21_Nucleotide_Duplication_on_the_α1__and_α2_Globin_Genes_Involves_a_Variety_of_Hypochromic_Microcytic_Anemias_From_Mild_to_Hb_H_Disease_ L2 - http://www.tandfonline.com/doi/full/10.3109/03630269.2015.1030757 DB - PRIME DP - Unbound Medicine ER -