DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia

• Published in: Scientific reports 2016-06, Vol.6 (1), p.26994-26994, Article 26994
• Main Authors: Tan, Jin Ai Mary Anne, Kho, Siew Leng, Ngim, Chin Fang, Chua, Kek Heng, Goh, Ai Sim, Yeoh, Seoh Leng, George, Elizabeth
• Format: Article
• Language: English
• Subjects: 45/23; 45/29; 45/77; 692/308; 692/699/1541; Adolescent; Adult; alpha-Thalassemia - diagnosis; alpha-Thalassemia - genetics; Child; Child, Preschool; DNA Mutational Analysis; Female; Hemoglobins, Abnormal - genetics; Heterozygote; Humanities and Social Sciences; Humans; Infant; Male; Molecular Diagnostic Techniques; multidisciplinary; Science; Science (multidisciplinary); Sequence Deletion
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep26994

Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α 3.7 ), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α codon 59 α/α CS α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α codon 59 α/α Paksé α) after nine years of being misdiagnosis with Hb Adana and HbCS (α codon 59 α/α CS α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.