Severe α-Thalassemia Intermedia Due to a Compound Heterozygosity for the Highly Unstable Hb Adana (HBA2: c.179G>A) and a Novel Codon 24 (HBA2: c.75T>A) Mutation

Abstract

We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

• α-globin gene
• α-Thalassemia (α-thal)
• nonsense mutation
• point mutation
• prenatal diagnosis

Acknowledgements

The authors thank the patients who were willing to be volunteers for this study, as well as Mewahyu Dewi (M. Biomed), Dr. Maria Dewi Indrawati and Dr. Widya Tirtha Kamandalu (The Eijkman Institute for Molecular Biology, Jakarta, Indonesia) for their helpful advice and encouragement during the preparation of this manuscript. The authors also sincerely thank Jan P. Schouten (MRC Holland) for providing the MLPA Kit and Al Harahap (Graduate Associate Teacher, Writing Program, University of Arizona, USA) for valuable comments, suggestions and proofreading the manuscript. Our thanks also to Dr. Baba Inusa [MRCP, FRCPCH, DCP (Haem), FMCPaed] (Evelina Children’s Hospital, Guy’s and St. Thomas’ National Health Service Foundation Trust, London, UK) for further suggestions and proofreading of the manuscript.