A Unique Interaction of IVS-I-1 (G>A) (HBA2: c.95+1G>A) with Hb Adana (HBA2: c.179G>A) Presenting as Transfusion-Dependent α-Thalassemia

• Published in: Hemoglobin 2018-07, Vol.42 (4), p.247-251
• Main Authors: Alauddin, Hafiza, Kamarudin, Khairina, Loong, Tang Yee, Azma, Raja Zahratul, Ithnin, Azlin, Jalil, Norunaluwar, Razak, Noor-Farisah, Koh-Xuan-Rong, Danny, Ismail, Endom, C-Khai, Loh, Abdul Latiff, Zarina, Alias, Hamidah, Othman, Ainoon
• Format: Article
• Language: English
• Subjects: alpha-Globins - genetics; alpha-Thalassemia - genetics; Child; Diagnosis, Differential; Erythrocyte Indices; Hb Adana (HBA2: c.179G>A); Hemoglobin A2 - genetics; Hemoglobins, Abnormal - genetics; Heterozygote; Humans; IVS-I-1 (G>A) (HBB: c.95+1G>A); Male; RNA Splice Sites; transfusion-dependent α-thalassemia (α-thal)
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1080/03630269.2018.1528985

Nondeletional α-globin mutations are known to cause more serious clinical effects than deletional ones. A rare IVS-I-1 (G>A) (HBA2: c.95+1G>A) donor splice site mutation interferes with normal splicing of pre mRNA and results in activation of a cryptic splice site as well as a frameshift mutation. Hb Adana [HBA2: c.179G>A (or HBA1)] is a highly unstable variant hemoglobin (Hb) resulting from a mutation at codon 59 on the HBA2 or HBA1 gene, recognized to cause severe α-thalassemia (α-thal) syndromes. We report a unique case of compound heterozygosity for these two mutations in a 9-year-old boy who presented with a Hb level of 5.3 g/dL and hepatomegaly at the age of 15 months. He required regular blood transfusions in view of a Hb level of