RESUMO
Hb Constant Spring [(Hb CS) alpha142, Term-->Gln (TAA>CAA in alpha2)] and Hb Koya Dora [alpha142, Term-->Ser (TAA>TCA in alpha2)] both involve mutations of the alpha2 gene stop codon and while Hb CS is the most frequent cause of nondeletional alpha-thalassemia (alpha-thal) in Southeast Asia, Hb Koya Dora is limited to a restricted population from Andhra Pradesh, India. Here we identify a homozygous case of Hb Koya Dora and confirm the structure of the 31 residue alpha chain extension.
Assuntos
Códon de Terminação/genética , Hemoglobinas Anormais/genética , Mutação , Talassemia alfa/genética , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Predisposição Genética para Doença/genética , Hemoglobinas Anormais/análise , Homozigoto , Humanos , Espectrometria de Massas por Ionização por Electrospray , Talassemia alfa/metabolismoRESUMO
The identification of a second case of Hb Fontainbleau [alpha21(B2)Ala-->Pro] allowed us to re-examine its association with microcytosis, explore the effects of the mutation on protein stability and define the mutation at a DNA level. Although slightly unstable, the variant was expressed at 28-29% of the total and was caused by a heterozygous mutation in the alpha2 gene. There was no evidence for concomitant alpha-thalassemia (alpha-thal); both alpha-globin gene deletion analysis and sequencing of the alpha-globin locus failed to detect any additional mutations that might explain the relatively high expression level.