title: 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: Department of Clinical Pathology, Seoul National University College of Medicine, Korea.
authors: J Y
authors: JY
authors: Kim
authors: S S
authors: SS
authors: Park
authors: S H
authors: SH
authors: Yang
authors: S I
authors: SI
authors: Joo
authors: Y J
authors: YJ
authors: Lee
authors: E K
authors: EK
authors: Ra
authors: S
authors: S
authors: Shin
authors: E C
authors: EC
authors: Kim
authors: H I
authors: HI
authors: Cho
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013163:Splenomegaly / Q000209:etiology; D017086:beta-Thalassemia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D012333:RNA, Messenger; C080993:hemoglobin Brescia; D005914:Globins