Ann Lab Med.  2012 Jan;32(1):99-101. 10.3343/alm.2012.32.1.99.

The First Study on Nucleotide-level Identification of Hb Koriyama in a Patient with Severe Hemolytic Anemia

• Park S
• Park JE
• Cho SI
• Jeon Y
• Park SS
• Seong MW

• KMID: 1781447
• DOI: http://doi.org/10.3343/alm.2012.32.1.99

Abstract

Hereditary hemolytic anemia comprises a group of disorders in which red blood cells are destroyed faster than they are produced in the bone marrow; various hereditary factors can cause this condition, including production of defective Hb and erythrocyte membrane. Recently, we identified Hb Koriyama, a rare Hb variant that was undetectable in Hb electrophoresis and stability tests, in a patient with severe hemolytic anemia. This is the first study to show the nucleotide-level sequence variations in Hb Koriyama. On the basis of our results, we conclude that unstable Hb may not be detectable by conventional Hb electrophoresis or stability tests. Thus, we suggest further genetic workup in cases of unexplained hereditary hemolytic anemia.

Keyword

Hemoglobinopathy; Hemoglobin variant; Hb Koriyama

MeSH Terms

Amino Acid Sequence
Anemia, Hemolytic/blood/*diagnosis
Child
Female
Gene Duplication
Hemoglobins, Abnormal/*genetics
Heterozygote
Humans
Molecular Sequence Data
Mutation
Sequence Analysis, DNA

Figure

• 

  Fig. 1 Results of the capillary zone electrophoresis showing decreased HbA levels (92.7%; reference interval, 96.8-97.8%), normal HbA2 levels (3.2%; reference interval, 2.2-3.2%), and increased HbF levels (4.1%; reference interval, ≤ 0.5%).

• 

  Fig. 2 Detailed characterization of the 15-bp duplication mutation identified in this study and the repeat sequence that flanks the duplication segment.

• 

  Fig. 3 Characteristics of aberrant amino acid sequences observed from the 15-bp duplication, and comparison of this duplication mutation with Hb Gun Hill, Hb Fairfax, and Hb Koriyama.

Reference

1. Natarajan K, Townes TM, et al. Kaushansky K, Lichtman MA, editors. Disorders of hemoglobin structure: sickle cell anemia and related abnormalities. Williams Hematology. 2010. 8th ed. New Yotk: McGraw-Hill.

2. Hardison RC, Chui DH, Giardine B, Riemer C, Patrinos GP, Anagnou N, et al. HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum Mutat. 2002. 19:225–233.

3. Giardine B, van Baal S, Kaimakis P, Riemer C, Miller W, Samara M, et al. HbVar database of human hemoglobin variants and thalassemia mutations: 2007 update. Hum Mutat. 2007. 28:206.

4. Patrinos GP, Giardine B, Riemer C, Miller W, Chui DH, Anagnou NP, et al. Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies. Nucleic Acids Res. 2004. 32:D537–D541.

5. Thein SL. Steinberg MH, Forget BG, editors. Structural variants with a β-thalassemia phenotype. Disorders of hemoglobin: genetics, pathophysiology, and clinical management. 2000. Cambridge: Cambridge University Press;342–355.

6. Kawata R, Ohba Y, Yamamoto K, Miyaji T, Makita R, Ohga K, et al. Hyperunstable hemoglobin Koriyama anti-Hb Gun Hill insertion of five residues in the beta chain. Hemoglobin. 1988. 12:311–321.

7. Steinberg MH, Forget BG, editors. Disorders of hemoglobin: genetics, pathophysiology, and clinical management. 2009. 2nd ed. Cambridge: Cambridgd University Press.

8. Rieder RF, Bradley TB Jr. Hemoglobin Gun Hill: an unstable protein associated with chronic hemolysis. Blood. 1968. 32:355–369.