title: The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience.
abstract: OBJECTIVE
  The spectrum of α-thalassemias correlates well with the number of affected α-globin genes. Additionally, combinations of the several non-deletional types of mutations with a large trans deletion comprising the 2 α-globin genes have an impact on the clinical severity. The objective of this study was to analyze the hematological and molecular data of 35 patients with Hb H disease from a single center in order to identify the genotypes of Hb H disease and genotype-phenotype correlations.
  
  
  METHODS
  Herein, we report the hematological and mutational spectrum of patients with Hb H disease (n=35). Additionally, genotypes of α-gene mutations of 78 individuals, who were referred to our institution for α-gene screening, were analyzed.
  
  
  RESULTS
  Supporting the previous data from Turkey, -α3.7 was the most common mutation among patients with Hb H disease (62.8%) and in the other 78 subjects (39.7%). Of the patients with Hb H disease, the most common genotypes were -α3.7/--20.5, -α3.7/--26.5, and -α3.7/--17.5 in 10 (28.6%), 6 (17.1%), and 6 (17.1%) patients, respectively. Another small deletion, -4.2 alpha, and several non-deletional types of α-gene mutations, namely α (-5nt): IVS-I donor site (GAG.GTG.AGG->GAG.G-----); α (PA-2): AATAAA>AATGGA, and α (cd59): GGC->GAC, were found to be associated with Hb H disease when present at trans loci of one of the large deletions given above. The combinations consisting of 1 non-deletional and 1 of the large deletional types of mutations (αTα/--) at trans loci were found to result in a more severe phenotype compared to the genotypes composed of 1 small trans deletion of a large deletion (-α/--). The combination of α (Cd59) and -- in trans was associated with severe phenotype and the disease was associated with an increase in Hb Bart's level with null Hb H. In spite of the presence of 2 intact α-globin genes, homozygosity for PA-2 mutation resulted in severe Hb H disease.
  
  
  CONCLUSIONS
  This study indicated that Hb H disease is not rare in Turkey and its genotype is quite heterogeneous.
authors: Hacettepe University Faculty of Medicine, Division of Pediatric Hematology, Ankara, Turkey Phone: +90 532 526 37 49 E-mail: suleunal@hacettepe.edu.tr.
authors: Şule
authors: Ş
authors: Ünal
authors: Fatma
authors: F
authors: Gümrük
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004909:Erythrocyte Indices; D017353:Gene Deletion; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006447:Hemoglobin H / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D017384:Sequence Deletion; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D055542:alpha-Globins; D006447:Hemoglobin H; C030448:hemoglobin Bart's