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

Hafiza Alauddin, Khairina Kamarudin, Yee Loong Tang, Raja Zahratul Azma Raja Sabudin, Azlin Ithnin, Norunaluwar Jalil, Noor Farisah Razak, Danny Koh-Xuan-Rong, Endom Ismail, C-Khai Loh, Zarina Abdul Latiff, Hamidah Alias, Ainoon Othman

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)247-251
Number of pages5
JournalHemoglobin
Volume42
Issue number4
DOIs
Publication statusPublished - 4 Jul 2018

Fingerprint

Thalassemia
Hemoglobins
Mutation
Erythrocyte Indices
RNA Splice Sites
Genes
Cells
Fathers
Hemoglobin H
Blood
Fetal Hemoglobin
Mothers
Globins
Polymerase chain reaction
RNA Precursors
Failure to Thrive
Frameshift Mutation
Hepatomegaly
Electrophoresis
Refractory materials

Keywords

  • Hb Adana (HBA2: c.179G>A)
  • IVS-I-1 (G>A) (HBB: c.95+1G>A)
  • transfusion-dependent α-thalassemia (α-thal)

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

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. / Alauddin, Hafiza; Kamarudin, Khairina; Tang, Yee Loong; Raja Sabudin, Raja Zahratul Azma; Ithnin, Azlin; Jalil, Norunaluwar; Razak, Noor Farisah; Koh-Xuan-Rong, Danny; Ismail, Endom; Loh, C-Khai; Abdul Latiff, Zarina; Alias, Hamidah; Othman, Ainoon.

In: Hemoglobin, Vol. 42, No. 4, 04.07.2018, p. 247-251.

Research output: Contribution to journalArticle

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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.",
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