Hb Oegstgeest [alpha104(G11)Cys-->Ser (alpha1)]. A new hemoglobin variant associated with a mild alpha-thalassemia phenotype.
A microcytic hypochromic anemic state was observed in an 8-year old Black female of Surinam origin during pre-operative Hb S [beta6(A3)Glu-->Val] screening. Her high zinc protoporphyrin (ZPP) level suggested a chronic iron depletion but, in contrast, the high red blood cell (RBC) count (5.85 x 10(12)/L) was indicative of a possible coexisting thalassemia. No abnormal hemoglobin (Hb) bands were present on high performance liquid chromatography (HPLC) or alkaline electrophoresis and the Hb A2 level was normal. Break point polymerase chain reaction (PCR) failed to reveal any of the common alpha-thalassemia (thal) mutations but selective DNA sequencing of both alpha-globin genes disclosed a TGC-->AGC transversion at codon 104 of the alpha1 gene. Cystine at codon 104 is involved in alpha/beta globin contact and has been described to be a critical amino acid of the alpha2 chain when substituted by a tyrosine (Hb Sallanches), inducing Hb H (beta4) disease in the homozygous state. Our heterozygous patient had a moderate anemia of 12.2 g/dL and a borderline haptoglobin suggesting some degree of hemolysis.
Harteveld
Cornelis L
CL
The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Rozendaal
Lieke
L
Blom
Nico A
NA
Lo-A-Njoe
Shirley
S
Akkerman
Nicole
N
Arkestijn
Sandra
S
Van Delft
Peter
P
Giordano
Piero C
PC
D019943:Amino Acid Substitution / Q000235:genetics*; D000747:Anemia, Hypochromic / Q000150:complications / Q000235:genetics*; D002648:Child; D003545:Cysteine / Q000235:genetics; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D012694:Serine / Q000235:genetics; D017085:alpha-Thalassemia / Q000150:complications / Q000235:genetics*
D006455:Hemoglobins, Abnormal; C506402:hemoglobin Oegstgeest; D012694:Serine; D003545:Cysteine