HEMOGLOBIN-S HEMOGLOBIN-OSLER - A CASE WITH 3 BETA-GLOBIN CHAINS - DNA-SEQUENCE (AAT) PROVES THAT HB-OSLER IS BETA-145 TYR-]ASN

A 13-year-old African-American female with erythrocytosis and three di fferent beta globins on electrophoresis beta(A), beta(S), and B-Osler, raised the possibility that one chromosome 11 might contain a duplica ted beta globin gene, since there are normally only 2 beta globin gene s. DNA sequence analysis showed GTG at codon 6 in exon 1, correspondin g to Hb S and AAT at codon 145 in exon 3, indicating a substitution of Asn for Tyr. Thus, Hb Osler undergoes spontaneous post-translational deamidation, beta 145 Asn-->beta 145 Asp. Unmodified Hb Osler (Asn) co -migrates with Hb A on electrophoresis and co-elutes with Hb A on HPLC ; therefore it has not been identified previously. All previous studie s have incorrectly identified the mutation as being beta 145 (HC 2) Ty r-->Asp. (C) 1996 Wiley-Liss, Inc.