IthaID: 88

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Context nucleotide sequence:
GGTGAACGTGGATGAAGTTGGTGGT [G>A] AGGCCCTGGGCAGGTTGGTATCAAG (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGKALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Comments: β codon 26 GAC>AAG [Glu>Lys] change gives rise to HbE, which also activates a cryptic splice site at the junction of exon 1 and intron 1 that causes abnormal alternative splicing and decreased transcription of functional mRNA for the HbE globin chain. Thus the Hb E mutation is both a qualitative defect (because of the amino acid substitution in the globin chain) and a quantitative defect with a β-thalassemia phenotype (because of decreased production of the mutated globin chain). Reduced Hb E synthesis explains Hb E levels in heterozygotes of between 25% to 30%. The homozygous state (Hb EE) manifests as a mild anemia with microcytes and target cells. Coihneritance with other hemoglobin variants (e.g., Hb S, forming Hb SE disease) or beta-thalassemia alleles (i.e., Hb E-β-thalassemia) creates a wide range of clinical severities. For example, Hb E-β0-thalassemia results in symptoms more severe than Hb EE and more closely resembles the severity of β-thalassemia major, requiring regular blood transfusions.

Heterozygous records (preview in IthaPhen)

1. Flatz G, Pik C, Sringam S, Haemoglobin E and beta-thalassaemia: their distribution in Thailand., Annals of human genetics, 29(2), 151-70, 1965 PubMed
2. Fairbanks VF, Oliveros R, Brandabur JH, Willis RR, Fiester RF, Homozygous hemoglobin E mimics beta-thalassemia minor without anemia or hemolysis: hematologic, functional, and biosynthetic studies of first North American cases., American journal of hematology, 8(1), 109-21, 1980 PubMed
3. Orkin SH, Kazazian HH, Antonarakis SE, Ostrer H, Goff SC, Sexton JP, Abnormal RNA processing due to the exon mutation of beta E-globin gene., Nature, 300(5894), 768-9, 1982 PubMed
4. Kazazian HH, Waber PG, Boehm CD, Lee JI, Antonarakis SE, Fairbanks VF, Hemoglobin E in Europeans: further evidence for multiple origins of the beta E-globin gene., American journal of human genetics, 36(1), 212-7, 1984 PubMed