title: A laboratory strategy for genotyping haemoglobin H disease in the Chinese.
abstract: BACKGROUND
  The thalassaemias are the commonest blood disorders worldwide, with South East Asia and southern China as areas of high prevalence. Accurate diagnosis of these disorders helps in clinical management with improved outcome.
  
  
  METHODS
  The alpha-globin genotypes of 100 Chinese patients in Hong Kong with haemoglobin H (Hb H) disease were characterised. Single-tube multiplex gap-PCR was used to detect --(SEA), -alpha(3.7) and -alpha(4.2), while Hb CS, Hb QS and codon 30 (DeltaGAG) were identified by single-tube multiplex amplification refractory mutation system (ARMS). Automated direct nucleotide sequencing of the amplified alpha2- and alpha1-globin genes was performed to characterise other non-deletional alpha-thalassaemia determinants.
  
  
  RESULTS
  In the 100 cases studied, 99 cases had --(SEA) in combination with deletional alpha(+)-thalassaemia or non-deletional alpha-globin gene mutation involving the alpha2-globin gene. In 70 cases of the deletional form, 43 cases showed the genotype of (--(SEA)/-alpha(3.7)) and 27 cases of (--(SEA)/-alpha(4.2)). Three of the 27 cases of (--(SEA)/-alpha(4.2)) were found to have Hb Q-Thailand linked in-cis with -alpha(4.2). The remaining 30 cases were of non-deletional form with the following genotypes: 11 cases of (--(SEA)/alpha(HbCS)alpha), 9 cases of (--(SEA)/alpha(HbQS)alpha), 3 cases of (--(SEA)/alpha(cd30 (DeltaGAG))alpha), 3 cases of (--(SEA)/alpha(cd31)alpha), 2 cases of (--(SEA)/alpha(poly-A)alpha), 1 case of (--(SEA)/alpha(HbWestmead)alpha) and 1 case of (--(non-SEA)/alpha(HbQS)alpha).
  
  
  CONCLUSIONS
  Based on two rapid diagnostic tests, multiplex gap-PCR and multiplex ARMS, more than 90% of the cases were genetically characterised. This laboratory strategy should be widely applicable for genetic diagnosis of alpha-thalassaemia.
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. achanjyu@pacific.net.hk
authors.forename: Amy Yuk-Yin
authors.initials: AY
authors.lastname: Chan
authors.forename: Chi-Chiu
authors.initials: CC
authors.lastname: So
authors.forename: Edmond Shiu-Kwan
authors.initials: ES
authors.lastname: Ma
authors.forename: Li-Chong
authors.initials: LC
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017353:Gene Deletion; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006447:Hemoglobin H / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006723:Hong Kong / Q000208:ethnology; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D017085:alpha-Thalassemia / Q000208:ethnology / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; C049214:hemoglobin Q Thailand; D005914:Globins; D006447:Hemoglobin H; C035541:Hemoglobin Constant Spring