Missense mutation of the last nucleotide of exon 1 (G->C) of globin gene not only leads to undetectable mutant peptide and transcript but also interferes with the expression of wild allele

* Hematology Division, University of Utah School of Medicine, Salt Lake City, UT; ° Hematology Division, Medical College of Georgia, Augusta, GA, USA; # Pediatric-Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA; @ ARUP Laboratories, Salt Lake City, UT, USA Correspondence: Josef T. Prchal, University of Utah, Hematology Division, 30 North 1900 East, Utah 4C416, Salt Lake City, USA. E-mail: josef.prchal{at}hsc.utah.edu Hemoglobin Monroe (β globin G->C, codon 30) is a missense mutation. We could not detect either the mutant peptide or transcript in reticulocyte-enriched preparation and in expanded erythroid progenitor cells. By quantitative gene expression assay β globin mRNA was found to be reduced by more than 70% in all heterozygous subjects with different haplotypes. We conclude that this mutation also interferes with expression of wild type allele.