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.

Abstract

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 <7.0 g/dL and failure to thrive. He had thalassemic red cell indices and peripheral blood film. The Hb electrophoresis only showed a raised Hb F level (3.3%) and a pre run peak but the Hb H inclusion test was negative. His father had thalassemic red cell indices but a normal Hb level. His mother had almost normal Hb levels and red cell indices. Hb Adana involving the HBA2 gene was detected by mutiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in the proband and his father. DNA sequencing of the HBA2 gene confirmed the IVS-I-1 mutation in the proband and his mother. This case highlighted the unique interaction of the IVS-I-1 mutation with Hb Adana in a young Malay boy presenting with transfusion-dependent α-thal.

• Authors: Hafiza Alauddin, Khairina Kamarudin, Tang Yee Loong, Raja Zahratul Azma, Azlin Ithnin, Norunaluwar Jalil, Noor-Farisah Razak, Danny Koh-Xuan-Rong, Endom Ismail, Loh C-Khai, Zarina Abdul Latiff, Hamidah Alias, Ainoon Othman
• Journal: Hemoglobin (Hemoglobin) Vol. 42 Issue 4 Pg. 247-251 (Jul 2018) ISSN: 1532-432X [Electronic] England
• PMID: 30623696 (Publication Type: Case Reports, Journal Article)

Chemical References

• Hemoglobins, Abnormal
• RNA Splice Sites
• alpha-Globins
• hemoglobin Adana
• Hemoglobin A2

Topics

• Child
• Diagnosis, Differential
• Erythrocyte Indices
• Hemoglobin A2 (genetics)
• Hemoglobins, Abnormal (genetics)
• Heterozygote
• Humans
• Male
• RNA Splice Sites
• alpha-Globins (genetics)
• alpha-Thalassemia (genetics)