title: Hb Zoetermeer: a new mutation on the alpha2 gene inducing an Ala-->Ser substitution at codon 21 is possibly associated with a mild thalassemic phenotype.
abstract: A 52-year-old Dutch male was referred to our laboratory for hemoglobinopathy analysis because of persistent microcytic hypochromic parameters and moderate erythrocytosis in the absence of iron deficiency. The hemoglobin (Hb) pattern was normal and breakpoint polymerase chain reaction (PCR) excluded the six common deletion defects of the alpha gene cluster. Direct sequencing revealed a GCT-->TCT transversion at codon 21 of the alpha2 gene generating an Ala-->Ser single amino acid substitution. The hematological parameters observed in the presence of this mutation are consistent with a compensated heterozygous alpha(+)-thalassemia (thal). However, the neutral mutation and the external position of the residue do not explain an association with this phenotype. Nevertheless, we cannot exclude that the mutation could induce the observed hematological abnormalities and could eventually be considered as a mutation associated with a mild alpha-thalassemic phenotype.
authors.affiliation: The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Willem C H
authors.initials: WC
authors.lastname: van Helden
authors.forename: George L
authors.initials: GL
authors.lastname: Boxma
authors.forename: Peter
authors.initials: P
authors.lastname: van Delft
authors.forename: Margaretha
authors.initials: M
authors.lastname: Bakker-Verweij
authors.forename: Henri
authors.initials: H
authors.lastname: Wajcman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Zanella-Cleon
authors.forename: Michel
authors.initials: M
authors.lastname: Becchi
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D019943:Amino Acid Substitution; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D013789:Thalassemia / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; C523160:hemoglobin Zoetermeer; D005914:Globins