Table 6. [Alpha-Thalassemia Carrier States]. - GeneReviews®

Term (Comment)	Genotype	Genotype-Phenotype Correlations
α-thalassemia trait/carrier (person is asymptomatic with microcytosis & mild anemia) ¹	Deletion/ inactivation of 2 α-globin genes	In cis (e.g., --/αα) ² In trans (e.g., -α/-α, -α^3.7/-α^3.7, -α^4.2/-α^4.2)	Deletion or inactivation of 2 α-globin genes in cis is assoc with slightly lower RBC indices than persons with 2-gene deletion in trans (-α/-α) due to compensatory increase of α-globin production from remaining HBA1.
Non-deletional inactivation of HBA2 globin gene	E.g., α^NDα/αα	Single-nucleotide variants are usually more severe than a 1-gene deletion due to lack of compensatory increase of α-globin production assoc with a 1-gene deletion. Moreover, pathogenic variants in HBA2 are more severe than those in HBA1 because HBA2 produces 2-3x more α-globin.
α-thalassemia silent carrier (completely silent hematologic phenotype or very mild microcytosis) ¹	Deletion of 1 α-globin gene	E.g., -α/αα, α-/αα	Completely silent hematologic phenotype or very mild microcytosis
Non-deletional inactivation of HBA1	E.g., αα^ND/αα	Because HBA1 produces 2x less α-globin than HBA2, pathogenic variants in HBA1 are assoc with a milder phenotype.

Term (Comment)

Genotype

Genotype-Phenotype Correlations

α-thalassemia trait/carrier
(person is asymptomatic with microcytosis & mild anemia) ¹

Deletion/
inactivation of 2 α-globin genes

In cis (e.g., --/αα) ²
In trans (e.g., -α/-α, -α^3.7/-α^3.7, -α^4.2/-α^4.2)

Deletion or inactivation of 2 α-globin genes in cis is assoc with slightly lower RBC indices than persons with 2-gene deletion in trans (-α/-α) due to compensatory increase of α-globin production from remaining HBA1.

Non-deletional inactivation of HBA2 globin gene

E.g., α^NDα/αα

Single-nucleotide variants are usually more severe than a 1-gene deletion due to lack of compensatory increase of α-globin production assoc with a 1-gene deletion.
Moreover, pathogenic variants in HBA2 are more severe than those in HBA1 because HBA2 produces 2-3x more α-globin.

α-thalassemia silent carrier
(completely silent hematologic phenotype or very mild microcytosis) ¹

Deletion of 1 α-globin gene

E.g., -α/αα, α-/αα

Completely silent hematologic phenotype or very mild microcytosis

Non-deletional inactivation of HBA1

E.g., αα^ND/αα

Because HBA1 produces 2x less α-globin than HBA2, pathogenic variants in HBA1 are assoc with a milder phenotype.

From: Alpha-Thalassemia

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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