title: Beta-thalassemia mutations in Singapore--a strategy for prenatal diagnosis.
abstract: The strategy for early prenatal diagnosis of beta-thalassemia in Singapore by direct detection of the mutant beta-globin gene requires the spectrum of mutations producing the disorder in this population to be characterized. We analyzed 134 beta-thalassemia alleles from Singapore by specific oligonucleotide hybridization after DNA amplification, using a nonradioactive enhanced chemiluminescence detection system. The mutations were identified in 90% of the alleles using five oligonucleotide probes for the following mutations: codons 41/42 (deletion-TCTT), IVS II nt 654 (C-->T), codon 17 (A-->T), IVS I nt 5 (G-->C), and -28 TATA box (A-->G). Together with the strategy of direct sequencing, a total of 97% of the mutations were identified. In the Chinese subpopulation, 97% of the mutations were detected by the oligonucleotide probes. Using just four oligonucleotide probes would identify 96% of the mutations, and 76% of the mutations were accounted for by codon 41/42 (-TCTT) and IVS II nt 654 (C-->T) mutations. Thus in this subpopulation early prenatal diagnosis would be possible in virtually all the affected families.
authors.affiliation: Department of Paediatrics, Singapore General Hospital.
authors.forename: I S
authors.initials: IS
authors.lastname: Ng
authors.forename: J B
authors.initials: JB
authors.lastname: Ong
authors.forename: C L
authors.initials: CL
authors.lastname: Tan
authors.forename: H Y
authors.initials: HY
authors.lastname: Law
mesh_terms: D000483:Alleles; D001483:Base Sequence; D002872:Chromosome Deletion; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011296:Prenatal Diagnosis; D012846:Singapore; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*