title: Detection and characterisation of beta-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China. scc@pathology.hku.hk
authors: C C
authors: CC
authors: So
authors: A C Y
authors: AC
authors: So
authors: A Y Y
authors: AY
authors: Chan
authors: S T Y
authors: ST
authors: Tsang
authors: E S K
authors: ES
authors: Ma
authors: L C
authors: LC
authors: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis; D017353:Gene Deletion; D005838:Genotype; D006453:Hemoglobinopathies / Q000208:ethnology / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D010641:Phenotype; D013789:Thalassemia / Q000235:genetics; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000208:ethnology / Q000235:genetics*
chemical_list: D055544:beta-Globins; D005319:Fetal Hemoglobin