title: Hb M Dothan [beta 25/26 (B7/B8)/(GGT/GAG-->GAG//Gly/Glu-->Glu]; a new mechanism of unstable methemoglobin variant and molecular characteristics.
abstract: A new unstable beta globin chain variant associated with methemoglobin (Met-Hb) phenotype was found in a Caucasian infant. Molecular analysis of the beta globin gene using polymerase chain reaction (PCR) amplification and sequencing led to the detection of a new in frame deletion in exon-1. Direct sequencing of the PCR product revealed a 3 bp deletion (-GTG) between codons 25/26, which resulted in the loss of a single amino acid (-Gly). We propose that this newly discovered unstable M-hemoglobin (M-Hb) variant, named Hb Dothan [GGT/GAG-->GAG//Gly/Glu-->Glu], is caused by a shift in the amino acid sequence and altered packing of the B and E helices during beta globin synthesis, and also changes the orientation of the critical proximal and distal histidine in the F and E helices respectively. Phenotype/Genotype features and molecular characteristics of this new beta chain are presented in this communication.
authors.affiliation: Sickle Cell Center, Medical College of Georgia, Augusta, GA 30912, USA. fkutlar@mcg.edu
authors.forename: F
authors.initials: F
authors.lastname: Kutlar
authors.forename: L M
authors.initials: LM
authors.lastname: Hilliard
authors.forename: L
authors.initials: L
authors.lastname: Zhuang
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.forename: B
authors.initials: B
authors.lastname: Eroglu
authors.forename: S E
authors.initials: SE
authors.lastname: Meiler
authors.forename: H
authors.initials: H
authors.lastname: Carmichael
authors.forename: R B
authors.initials: RB
authors.lastname: Russell
authors.forename: A
authors.initials: A
authors.lastname: Kutlar
mesh_terms: D005091:Exons / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008706:Methemoglobin / Q000737:chemistry / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D017384:Sequence Deletion; D055544:beta-Globins / Q000235:genetics*
chemical_list: D055544:beta-Globins; D008706:Methemoglobin