ABSTRACT
We report in this paper a novel thalassemia mutation (insertion of a single A nucleotide within the exon 1, at codon 18, of the beta-globin gene) associated with a deletion of the deltabeta-globin gene region, in a patient exhibiting high persistence of fetal hemoglobin. The novel mutation causes a frameshift with the generation of a UGA stop codon. Analysis of the parent's DNA demonstrates that the A insertion and frameshift mutation are inherited from the father, while the deltabeta-globin gene deletion is inherited from the mother. Gene dosage analysis and deletion-specific PCR demonstrate that the deletion is the (deltabeta)(0) Sicilian deletion, involving a 13.4-kb deltabeta-globin gene region.
Subject(s)
Codon , Fetal Hemoglobin/genetics , Frameshift Mutation , Globins/genetics , Thalassemia/genetics , Cells, Cultured , Child , Chromatography, High Pressure Liquid , DNA/genetics , Exons , Female , Gene Deletion , Gene Dosage , Humans , Immunohistochemistry , Molecular Sequence Data , Phenotype , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
Results from a collaborative exercise with proficiency testing conducted by 20 Italian laboratories on the 15 loci included in the Identifiler kit were analyzed by allele sharing methods and by standard population genetics tests. The validated database, including about 1500 subjects, was merged with that of a previous exercise conducted on nine loci, and the resulting allele frequencies, subdivided by Italian region, were published on-line.
