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.


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.
So
C C
CC
Department of Pathology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China. scc@pathology.hku.hk
So
A C Y
AC
Chan
A Y Y
AY
Tsang
S T Y
ST
Ma
E S K
ES
Chan
L C
LC
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*
D055544:beta-Globins; D005319:Fetal Hemoglobin