Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease.

Area of Science:

• Genetics
• Hematology

Background:

• Alpha-thalassemia (α-thal) is typically moderate, but severe forms exist.
• Severe α-thal often necessitates regular blood transfusions.

Observation:

• Two Chinese families with transfusion-dependent Hb H disease were studied.
• Rare mutations in the α-globin genes (HBA1, HBA2) were investigated.

Findings:

• Hb Zürich-Albisrieden mutation in HBA1, combined with the Southeast Asian deletion (- -^SEA), caused severe α-thal.
• A novel variant, Hb Sichuan (HBA1: c.393_394insT), also led to severe α-thal when associated with the - -^SEA deletion.

Implications:

• These HBA1 mutations can result in continuous blood transfusion-dependent α-thal.
• Carrier detection is vital, particularly for couples with a known α⁰-thal carrier partner.