Hb Stara Zagora: a new hyper-unstable hemoglobin causing severe hemolytic anemia.
We describe a new hyper-unstable beta chain variant (codons 137-139, -6 bp) in a 2-year-old Bulgarian boy. The abnormal hemoglobin (Hb) is associated with severe hemolytic anemia as a consequence of its hyper instability. The child was admitted to the Pediatric Clinic (Faculty of Medicine, Stara Zagora, Bulgaria) at the age of 2 months. Because of anemia (Hb 6.9 g/dL) and high serum iron level (58 microM/L) the child was transfused. However, a month later his Hb level had dropped to 7.5 g/dL, and since then he has been on a regular monthly blood transfusion regimen. Hemoglobin analysis of a blood sample collected 2 months after the last transfusion at the age of 2 years, revealed no abnormalities except for the presence of inclusion bodies after incubation of peripheral blood with brilliant cresyl blue. Sequencing of the beta-globin gene revealed heterozygosity for a 6 bp deletion (-TGGCTA) at codons 137 [the second and third base pair (bp)], 138 and 139 (the first bp), forming a new codon at position 137 (GAT). This event eliminates three amino acids (Val-Ala-Asn) and introduces a new residue (Asp). It creates a new restriction site for HphI. The parents and his dizygotic twin brother had no history of hemolysis. The paternity of the child was confirmed by DNA analysis.
Petkov
Georgi H
GH
Pediatric Clinic, Faculty of Medicine, Stara Zagora, Bulgaria.
Simjanovska
Liljana
L
Tchakarova
Petranka
P
Efremov
Georgi D
GD
D000743:Anemia, Hemolytic / Q000235:genetics*; D004252:DNA Mutational Analysis; D015257:DNA-Cytosine Methylases; D005192:Family Health; D014644:Genetic Variation; D006454:Hemoglobins / Q000032:analysis; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007501:Iron / Q000097:blood; D008297:Male; D017384:Sequence Deletion
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; C508158:hemoglobin Stara Zagora; D007501:Iron; C057825:DNA modification methylase NgoBI; D015257:DNA-Cytosine Methylases