title: A novel (A)γδβ(0)-thalassemia caused by DNA deletion-inversion-insertion of the β-globin gene cluster and five olfactory receptor genes: Genetic interactions, hematological phenotypes and molecular characterization.
abstract: OBJECTIVE
  To report the phenotypes and genetic basis of a novel (A)γδβ(0)-thalassemia found in Thai individuals with several forms of thalassemia.
  
  
  METHODS
  An initial study was done in an adult Thai woman who had hypochromic microcytic red cells with unusually 100% Hb F. Extended study was carried out on her parents and another 17 unrelated individuals with elevated Hb F. Hb analysis was performed by capillary electrophoresis and DNA analysis was done using PCR. A novel diagnostic method based on multiplex PCR assays was developed.
  
  
  RESULTS
  DNA analysis of the proband revealed the homozygosity for a novel deletion of 118.3 kb, removing the entire (A)γ, ψβ, δ-, β-globin and five olfactory receptor (OR) genes with an insertion of a 179 bp inverted DNA sequence located behind the OR52A5 gene located downstream and an insertion of 7 orphan nucleotides. Her parents were both carriers of this mutation. Further screening in suspected cases in our series unexpectedly led to identification of an additional 17 cases with this mutation in different genotypes including plain heterozygote, homozygote, compound heterozygote with Hb E, and double heterozygote with several forms of α-thalassemia. Hematological features associated with these genetic interactions are presented.
  
  
  CONCLUSIONS
  Haplotype analysis indicated a single origin of this novel deletion-inversion-insertion (A)γδβ(0)-thalassemia in the Thai population. Differentiation of this mutation and other high Hb F determinants documented previously could be done by using a developed multiplex PCR assay.
authors: The Medical Science Program, Graduate School, Khon Kaen University, Thailand; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors: Kritsada
authors: K
authors: Singha
authors: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand.
authors: Goonnapa
authors: G
authors: Fucharoen
authors: Narathiwasrajanagarindra Hospital, Narathiwas, Thailand.
authors: Abdulloh
authors: A
authors: Hama
authors: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Thailand. Electronic address: supan@kku.ac.th.
authors: Supan
authors: S
authors: Fucharoen
mesh_terms: D000328:Adult; D001483:Base Sequence; D007446:Chromosome Inversion / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D016254:Mutagenesis, Insertional; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055538:delta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D055544:beta-Globins
keywords: (A)γδβ(0)-Thalassemia; Hereditary persistence of fetal hemoglobin (HPFH); High hemoglobin F determinant; Olfactory receptor gene deletion