title: Unbiased analysis of the frequency of beta-thalassemia point mutations in a population of African-American newborns.
abstract: OBJECTIVE
  To determine frequency of specific beta-thalassemia alleles in the African-American population prospectively, using newborn screening specimens, and to evaluate the need for including these alleles in screening follow-up programs.
  
  
  METHODS
  Allele-specific oligonucleotide tests were developed and used to analyze African-American newborn screening specimens for beta-thalassemia point mutations to determine their frequency. Direct sequencing of amplified DNA from the dried blood specimens was used to confirm the presence of point mutations.
  
  
  METHODS
  African-American newborns in Texas.
  
  
  RESULTS
  Allele-specific oligonucleotides identified five newborn specimens carrying beta-thalassemia point mutations among 471 specimens from African-American neonates. Direct sequencing of DNA from the dried blood specimens confirmed that these individuals had a normal and a mutant allele. Five newborn screening specimens in which the results of screening and DNA tests were in disagreement (four with FS by screening and AS by DNA, and one with FC by screening and AC by DNA) were analyzed for these beta-thalassemia point mutations and in each case were found to be S/beta-thalassemia or C/beta-thalassemia compound heterozygotes, respectively.
  
  
  CONCLUSIONS
  Allele-specific oligonucleotides accurately identified newborn specimens carrying beta-thalassemia point mutations. Direct sequencing from dried blood specimens confirmed these results. The A(-29)G allele frequency was 0.003, and the C(-88)T frequency was 0.002. These alleles also were observed among positive samples in a neonatal hemoglobinopathy screening program. Therefore, any newborn screening program with a molecular genetic follow-up component must include testing for these beta-thalassemia alleles to assure timely and appropriate management for affected infants.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Tex. 77030.
authors.forename: D A
authors.initials: DA
authors.lastname: Sylvester-Jackson
authors.forename: S L
authors.initials: SL
authors.lastname: Page
authors.forename: J M
authors.initials: JM
authors.lastname: White
authors.forename: H M
authors.initials: HM
authors.lastname: McCabe
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: B L
authors.initials: BL
authors.lastname: Therrell
authors.forename: E R
authors.initials: ER
authors.lastname: McCabe
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015982:Bias; D044383:Black People / Q000235:genetics*; D004247:DNA / Q000097:blood; D006801:Humans; D007231:Infant, Newborn / Q000097:blood; D008969:Molecular Sequence Data; D015997:Neonatal Screening; D009693:Nucleic Acid Hybridization; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017086:beta-Thalassemia / Q000208:ethnology / Q000235:genetics*; D001741:Black or African American
chemical_list: D004247:DNA