title: Genetic diversity of beta-thalassemia mutations in Pakistani population.
abstract: BACKGROUND
  beta-thalassemia is one of the most common inherited single gene disorder in Pakistan. It is characterized by reduced or absent beta-globin gene expression resulting in abnormal maturation and survival of red blood cells. Due to high prevalence of this disease in the local population, it has become important for the health care providers to encourage people to utilize laboratory facilities for carrier and prenatal genetic testing.
  
  
  OBJECTIVE
  To study the frequency of beta-thalassemia mutations in Pakistani population.
  
  
  METHODS
  A tertiary care teaching hospital.
  
  
  METHODS
  Blood samples of 72 couples and chorionic villus (CV) biopsy specimen collected at the Aga Khan University Hospital, Karachi were tested by Amplified Refractory Mutation Systems (ARMS) for the 12 most common mutations in the beta-globin gene.
  
  
  RESULTS
  Out of 72 chorionic villus biopsy specimen analyzed, 17 (23%) had mutations in both alleles of the beta-globin gene. Homozygosity was identified in 6 CV samples, whereas 11 CV specimens were diagnosed as double heterozygous. Almost 60% of the CV biopsies showed mutations in one allele and were diagnosed as carriers. IVSI-5 (G-C) was the most common mutation identified in this study. It was found in 53% of the subjects and was represented equally in all the ethnic groups except Pathans. Several regional and ethnic differences were observed in the distribution of common mutations, for example in Pathan families Fr 8-9 (+G) mutation was most prevalent. In addition, variation in the distribution of mutations was also observed between the Northern and the Southern regions.
  
  
  CONCLUSIONS
  This study indicates that in Pakistan, the five most common mutations are IVS1-5 (G-C), IVS1-1 (G-T), Fr 41-42 (-TTCT) Fr 8-9 (+G) and deletion 619 bp. An important factor contributing to high incidence of thalassemia is the unawareness among people about the available diagnostic facilities for the prenatal diagnosis in Pakistan. Strict implementation of collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing beta-thalassemia in Pakistan.
authors.affiliation: Department of Pathology, Aga Khan University Hospital, Karachi.
authors.forename: B
authors.initials: B
authors.lastname: Khateeb
authors.forename: T
authors.initials: T
authors.lastname: Moatter
authors.forename: A M
authors.initials: AM
authors.lastname: Shaghil
authors.forename: S
authors.initials: S
authors.lastname: Haroon
authors.forename: G N
authors.initials: GN
authors.lastname: Kakepoto
mesh_terms: D000328:Adult; D015152:Blotting, Northern; D015139:Blotting, Southern; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009154:Mutation; D010154:Pakistan / Q000453:epidemiology; D011247:Pregnancy; D011295:Prenatal Care; D015995:Prevalence; D017086:beta-Thalassemia / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*