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

• Published in: Journal of clinical pathology Vol. 62; no. 12; pp. 1107 - 1111
• Main Authors: So, C C, So, A C Y, Chan, A Y Y, Tsang, S T Y, Ma, E S K, Chan, L C
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Association of Clinical Pathologists 01.12.2009; BMJ Publishing Group
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; beta-Globins - genetics; beta-Thalassemia - ethnology; beta-Thalassemia - genetics; Biological and medical sciences; Child; Child, Preschool; Female; Fetal Hemoglobin - analysis; Gene Deletion; Genotype; Hemoglobinopathies - ethnology; Hemoglobinopathies - genetics; Humans; Infant; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Multigene Family - genetics; Nucleic Acid Amplification Techniques - methods; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Phenotype; Thalassemia - genetics; Young Adult; Asia; China; Gene cluster; Anatomic pathology; Multiplex ligation dependent probe amplification; Beta-Peptide chain; Deletion; Chinese; Beta globin; Diagnosis; Detection
• DOI: 10.1136/jcp.2009.067538
• ISSN: 0021-9746; 1472-4146

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.