HB HINWIL OR BETA-38(C4)THR-]ASN - A NEW BETA-CHAIN VARIANT DETECTED IN A SWISS FAMILY

This paper reports a new hemoglobin variant which was identified while investigating the cause of a mild erythrocytosis. The abnormal beta-g lobin chain was detected by reversed phase chromatography. Mutation ma pping of the beta-globin gene by polymerase chain reaction and denatur ing gradient gel electrophoresis followed by sequence analysis reveale d a C-->A transversion at codon 38, predicting a Thr-->Asn substitutio n. Tryptic peptide mapping by liquid chromatography electrospray mass spectrometry, followed by conventional Edman peptide sequence analysis , confirmed the predicted amino acid substitution. In contrast to the only other known mutation at codon 38, Hb Hazebrouck (Thr-->Pro), this hemoglobin is stable and shows elevated oxygen affinity.