CORRESPONDENCE 2791 HEMOGLOBIN CHESTERFIELD (828 LEU + ARG) PRODUCES THE PHENOTYPE OF INCLUSION BODY 8 THALASSEMIA

To the Editor: peak (p”) eluting after the normal PA chain (Fig 1A). The total radioactivity of dPA + p ” was 1.64 while dPA was 2.47 and P” Several dominant forms of p thalassemia have recently been accounted for 33 % of the total p chains after 60 minutes of identified that result in a thalassemia intermedia phenotype in incubation. No abnormal Hb was detected by heat denaturation or individuals who have inherited only a single copy of the abnormal f3 isopropanol tests. gene.’’6 We describe here an individual with severe heterozygous p Analysis of seven restriction fragment length polymorphisms thalassemia characterized by large inclusion bodies in the periph- (RFLPs) in the p-globin gene cluster showed: HindII-c-/-, eral blood associated with a single-base substitution, CTG-+ HindIII-‘yiAy +-/--, HindII-Jrp, 3‘Jrp ++/--, AvaII-P +/+ CGG, in codon 28 of the p gene. This novel mutation, which is and BamHI-p +/-. Heterozygosity for five of these sites indicates found in exon 1, leads to the synthesis of an unstable pvariant, p28 the absence of a major rearrangement or deletion. a-globin gene Leu + A r g (hemoglobin [Hb] Chesterfield). mapping showed a normal a-genotype (adaa). The P-globin genes The patient was a 34-year-old English woman who presented at were.enzymatically amplified by the polymerase chain reaction the age of 7 years with abdominal pain and was found to be anemic (PCR) and directly sequenced as previously described. ’ Direct and jaundiced with hepatosplenomegaly. She received sporadic genomic sequencing of 2,100 base pairs (bp) of the p-globin genes, blood transfusions but became transfusion-dependent at the age of extending from 307 bp upstream of the Cap site to 320 b