Background: Deletions in the β-globin cluster causing thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) are uncommon and difficult to detect. Data in Chinese are very scarce.
Aims: To use a recently available technique to investigate the frequencies and nature of β-globin cluster deletions in Chinese.
Methods: 106 subjects with phenotypes of thalassaemia or HPFH and suspected to have deletions in the β-globin cluster were studied. A commercially available kit employing multiplex ligation-dependent probe amplification (MLPA) was used to screen for deletions. Gap PCR and direct nucleotide sequencing were used to characterise deletions detected.
Results: 17 deletions in the β-globin cluster were found in 17 patients: 8 of Chinese (Aγδβ)0 thalassaemia, 7 of Southeast Asian (Vietnamese) deletion and 2 of Thai (Aγδβ)0 thalassaemia. The only type of deletion detected in δβ-thalassaemia was Chinese (Aγδβ)0 thalassaemia. The deletional form of HPFH was rarely seen in only 1 case of Thai (Aγδβ)0 thalassaemia. Deletions presenting as β-thalassaemia trait and raised HbF were all of the Southeast Asian (Vietnamese) deletion type. When these deletions were co-inherited with classical β-thalassaemia mutations in compound heterozygous states, the phenotypes could be very variable.
Conclusions: In the Chinese population, there are only relatively few types of deletions seen in the β-globin cluster. MLPA is a fast and effective way of screening for these deletions. Characterisation of these deletions allows the development of simpler and more specific PCR-based tests for routine diagnostic use. Accurate prediction of phenotype is not always feasible. The molecular defects in many cases of HPFH still await discovery.
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Supplementary data is published online only at http://jcp.bmj.com/content/vol62/issue12
Funding This work was supported by a grant from the Children’s Thalassaemia Foundation of Hong Kong (project no. 2007/03).
Competing interests None.
Ethics approval Not applicable. Reason: All 102 patient samples were initially taken with proper consent for globin study during diagnostic workup which includes phenotyping and genotyping. The four subjects recruited from an ongoing genetic association study have given written consent and ethical approval has been obtained for genotyping.
Provenance and peer review Not commissioned; externally peer reviewed.