Detection and characterisation of beta-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification.

BACKGROUND Deletions in the beta-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 beta-globin cluster deletions in Chinese. METHODS 106 subjects with phenotypes of thalassaemia or HPFH and suspected to have deletions in the beta-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 beta-globin cluster were found in 17 patients: 8 of Chinese ((A)gammadeltabeta)(0) thalassaemia, 7 of Southeast Asian (Vietnamese) deletion and 2 of Thai ((A)gammadeltabeta)(0) thalassaemia. The only type of deletion detected in deltabeta-thalassaemia was Chinese ((A)gammadeltabeta)(0) thalassaemia. The deletional form of HPFH was rarely seen in only 1 case of Thai ((A)gammadeltabeta)(0) thalassaemia. Deletions presenting as beta-thalassaemia trait and raised HbF were all of the Southeast Asian (Vietnamese) deletion type. When these deletions were co-inherited with classical beta-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 beta-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.