title: The clinical significance of the spectrum of interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians.
abstract: OBJECTIVE
  To assess the clinical significance of the interactions of CAP+1 (A-->C), a silent beta-globin gene mutation, with other beta-thalassemia mutations and globin gene modifiers in north Indians.
  
  
  METHODS
  The clinical phenotypes associated with compound heterozygosity for the CAP+1 (A-->C) mutation with other beta-thalassemia mutations, together with the potential effect of the genetic modifiers alpha-thalassemia and the Xmn-1(G)gamma C-->T polymorphism were studied in 30 patients. The frequency of the CAP+1 (A-->C) polymorphism was determined and an analysis of the red cell indices, HbA(2) levels, iron status, and alpha-globin genes was carried out in 35 heterozygotes.
  
  
  RESULTS
  Based on an analysis of 1075 beta-thalassemia alleles the CAP+1 (A-->C) mutation constituted 3.2% of north Indians. There was a wide spectrum of phenotypic severity in compound heterozygotes; 18 of 30 were transfusion dependent. There was a very high frequency of the -/- genotype of the Xmn-1(G)gamma polymorphism in compound heterozygotes. Analysis of 35 heterozygotes indicated that approximately half were hematologically normal and therefore genuine 'silent' carriers.
  
  
  CONCLUSIONS
  Compound heterozygotes for CAP+1 (A-->C) and other severe beta-thalassemia alleles are phenotypically severe enough to necessitate appropriate therapy and counseling. The unexpected severity of these interactions may be due, in part, to the high frequency of beta-thalassemia alleles associated with the Xmn-1(G)gamma- allele in Indian populations. It is concluded that the CAP+1 (A-->C) mutation can pose serious difficulties in screening and counseling programs in populations in which it occurs at a significant frequency.
authors: Department of Haematology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors: Gurjeewan
authors: G
authors: Garewal
authors: Reena
authors: R
authors: Das
authors: Anshu
authors: A
authors: Awasthi
authors: Jasmina
authors: J
authors: Ahluwalia
authors: Ram Kumar
authors: RK
authors: Marwaha
mesh_terms: D000225:Adenine; D000293:Adolescent; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003596:Cytosine; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005914:Globins / Q000235:genetics*; D006443:Hemoglobin A2 / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D008297:Male; D008403:Mass Screening; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D017086:beta-Thalassemia / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*
chemical_list: C489549:CAP1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D003596:Cytosine; D005914:Globins; D006443:Hemoglobin A2; D000225:Adenine