A Korean family with a dominantly inherited beta-thalassemia due to Hb Durham-N.C./Brescia.

Abstract

We describe the molecular and the hematological characteristics of a Korean family with a dominantly inherited beta-thalassemia. Carriers were characterized by moderate anemia, hypochromia, microcytosis, elevated Hb A2 and Hb F levels, and splenomegaly. DNA analysis revealed a CTG (Leu) to CCG (Pro) substitution at codon 114 of the beta-globin gene, that leads to a highly unstable hemoglobin variant, Hb Durham-N.C./Brescia, and this was linked to the beta haplotype V, [+----+-], and framework 2. RNA analysis showed that the proband had comparable levels of mutant and normal beta-mRNA. Translation of the mutant mRNA would give rise to non-functional hyperunstable beta-globin chains, and their degradation would, by placing an additional burden on the proteolytic process of the red blood cell precursors, result in a more severe phenotype.

• Authors: J Y Kim, S S Park, S H Yang, S I Joo, Y J Lee, E K Ra, S Shin, E C Kim, H I Cho
• Journal: Hemoglobin (Hemoglobin) Vol. 25 Issue 1 Pg. 79-89 (Feb 2001) ISSN: 0363-0269 [Print] England
• PMID: 11300352 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon
• Hemoglobins, Abnormal
• RNA, Messenger
• hemoglobin Brescia
• Globins

Topics

• Adolescent
• Adult
• Amino Acid Substitution
• Codon (genetics)
• DNA Mutational Analysis
• Female
• Genes, Dominant
• Globins (genetics)
• Haplotypes (genetics)
• Hemoglobins, Abnormal (analysis, genetics)
• Heterozygote
• Humans
• Korea (epidemiology)
• Male
• Middle Aged
• Mutation, Missense
• Phenotype
• Protein Biosynthesis
• RNA, Messenger (biosynthesis)
• Splenomegaly (etiology)
• beta-Thalassemia (epidemiology, genetics)