title: Clinical, hematologic and molecular variability of sickle cell-β thalassemia in western India.
abstract: BACKGROUND
  Sickle cell-β thalassemia (HbS-β thalassemia) is a sickling disorder of varying severity, which results from compound heterozygosity for sickle cell trait and β thalassemia trait. The present study was undertaken to determine the genetic factors responsible for the clinical variability of HbS-β thalassemia patients from western India.
  
  
  METHODS
  Twenty-one HbS-β thalassemia cases with variable clinical manifestations were investigated. The α and β globin gene clusters were studied by molecular analysis.
  
  
  RESULTS
  Thirteen patients showed milder clinical presentation as against eight patients who had severe clinical manifestations. Four β thalassemia mutations were identified: IVS 1-5 (G→C), codon 15 (G→A), codon 30 (G→C) and codon 8/9 (+G). α thalassemia and XmnI polymorphism in homozygous condition (+/+) were found to be common among the milder cases. The β(S) chromosomes were linked to the typical Arab-Indian haplotype (#31). Framework (FW) linkage studies showed that four β thalassemia mutations were associated with different β globin gene frameworks. Linkage of codon 15 (G→A) mutation to FW2 is being observed for the first time.
  
  
  CONCLUSIONS
  The phenotypic expression of HbS-β thalassemia is not uniformly mild and α thalassemia and XmnI polymorphism in homozygous condition (+/+) are additional genetic factors modulating the severity of the disease in the Indian subcontinent.
authors.affiliation: Department of Hemato-Genetics, National Institute of Immunohaematology (ICMR), Mumbai, India.
authors.forename: Malay B
authors.initials: MB
authors.lastname: Mukherjee
authors.forename: Anita H
authors.initials: AH
authors.lastname: Nadkarni
authors.forename: Ajit C
authors.initials: AC
authors.lastname: Gorakshakar
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Dipika
authors.initials: D
authors.lastname: Mohanty
authors.forename: Roshan B
authors.initials: RB
authors.lastname: Colah