title: Prenatal diagnosis of unusual hemoglobinopathies.
abstract: While analyzing 280 hemoglobinopathy kindreds with prescribed molecular tests, 3 unusual mutations were observed that required additional characterization. In the first case, the hypervariable region flanking the alpha-globin genes generated an intermediate length 8.2 kb psi zeta-globin gene fragment on a Southeast Asian chromosome with two deleted alpha-globin genes. Rehybridization of the Southern blot with alpha-globin probe distinguished the mutation unambiguously. In the second case, restriction enzyme analysis of a PCR amplified black beta-globin gene detected a novel beta-83 point mutation adjacent to a promoter element. In the third case, which was uninformative with available allele specific oligonucleotides (ASOs), total genomic PCR amplification and sequencing identified a single basepair insertion in codon 36/37 of an Iranian beta-globin gene that shifted the reading frame and obliterated gene activity. Developing additional region-specific ASOs will further diminish the number of cases that must be characterized by genomic PCR sequencing.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco 94143-0720.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: R V
authors.initials: RV
authors.lastname: Lebo
authors.forename: S P
authors.initials: SP
authors.lastname: Cai
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.forename: W C
authors.initials: WC
authors.lastname: Mentzer
authors.forename: M S
authors.initials: MS
authors.lastname: Golbus
mesh_terms: D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000235:genetics; D001483:Base Sequence; D015193:Chorionic Villi Sampling; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D016368:Frameshift Mutation; D017353:Gene Deletion; D006239:Haplotypes; D006453:Hemoglobinopathies / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics
chemical_list: D017931:DNA Primers; D015345:Oligonucleotide Probes