Copy number variations of six and seven α-globin genes in a family with intermedia and major thalassemia phenotypes.
BACKGROUND
Copy number variations in α-globin genes are results of unequal crossover between homologous segments in the α-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of α-globin genes leads to imbalance of α/β chains in hemoglobin tetramer and consequently attenuate or worsen the β-thal clinical symptoms, respectively.


OBJECTIVE
Multiplications in α-globin genes have been found in some populations, justifying unexpected severe phenotype of β-thal carriers.


METHODS
Unexpected severe phenotype in the family members may result from coexistence of extra α-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous β-thalassemia.


RESULTS
We described different multiplications in α-globin locus in an Iranian family with one, two or three extra α-globin genes (ααα/αα, αααα/αα and αααα/ααα).


CONCLUSIONS
The excess α-globin gene/genes cause increment in β/α chain imbalance and leads to worsening pathophysiology and clinical severity of β-thalassemia carriers.
a 1 Genetics Research Center, University of Social Welfare & Rehabilitation Sciences, Tehran, Iran.
Samaneh
S
Farashi
Shadi
S
Vakili
Negin
N
Faramarzi Garous
Mehri
M
Ashki
Hashem
H
Imanian
Azita
A
Azarkeivan
Hossein
H
Najmabadi
D056915:DNA Copy Number Variations; D018628:Gene Dosage; D020440:Gene Duplication; D015321:Gene Rearrangement; D056426:Genetic Loci; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D005810:Multigene Family; D009154:Mutation; D010641:Phenotype; D012720:Severity of Illness Index; D055542:alpha-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics*
D055542:alpha-Globins
Iranian; copy number variation; gametogenesis; α-globin gene cluster; β-thalassemia carrier