Severe hemolytic anemia associated with Hb Volga [beta27(B9)Ala-->Asp]: GCC-->GAC at codon 27 in a Turkish family.
A boy presented at age 4 years with severe congenital hemolytic anemia characterized by highly elevated reticulocyte count (30-50%) and prominent basophilic stippling. Hb had been 4 g/dL at age 7 months. The patient was on a monthly transfusion regimen up to the age of 7 years, when he underwent splenectomy. After removal of the spleen, his Hb stabilized at 11 g/dL. No abnormal pattern was detected in hemoglobin electrophoresis at pH 9 and 6. In-vitro globin synthesis revealed the presence of an abnormal beta-chain in front of the gamma-chain. The beta(A)/beta(X) ratio was 0.77 at 30 min and 0.74 at 2 hr of incubation. Molecular analysis revealed that the patient had GCC-->GAC alteration at codon 27 (beta27(B9)Ala-->Asp) causing the abnormal hemoglobin Volga. The beta-cDNA derived from the beta-Hb Volga allele could be differentiated from HbA beta-cDNA on silver-stained gel. No imbalance in the mRNA of beta(A)/beta(Hb Volga) ratio was observed.
Sözen
M
M
Department of Molecular Biology, Faculty of Science, Hacettepe University, Ankara, Turkey.
Karaaslan
C
C
Oner
R
R
Gümrük
F
F
Ozdemir
M A
MA
Altay
C
C
Gürgey
A
A
Oner
C
C
D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D001797:Blood Protein Electrophoresis; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D003131:Combined Modality Therapy; D003676:Deferoxamine / Q000627:therapeutic use; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005914:Globins / Q000235:genetics; D006455:Hemoglobins, Abnormal / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000209:etiology; D017701:Reticulocyte Count; D016622:Silver Staining; D013156:Splenectomy; D013927:Thrombosis / Q000209:etiology; D014421:Turkey
D003062:Codon; D006455:Hemoglobins, Abnormal; D007502:Iron Chelating Agents; C045643:hemoglobin Volga; D005914:Globins; D015252:Deoxyribonucleases, Type II Site-Specific; C024403:GGCC-specific type II deoxyribonucleases; D003676:Deferoxamine