title: Hb Amsterdam [alpha32(B13)Met--Ile (alpha2)]: a new unstable variant associated with an alpha-thalassemia phenotype and a new African polymorphism.
abstract: We have characterized a new abnormal hemoglobin (Hb) at position 32 of the alpha-globin chain. The proband, a 38-year-old woman of Surinamese Black ancestry, was referred to the Academic Hospital in Amsterdam, The Netherlands, after 3 years of Prednisone treatment in Surinam. Kidney failure was diagnosed at the Nephrology Department, Free University Medical Center, Amsterdam, The Netherlands; the cortisone treatment was interrupted and dialysis was started. At this stage, a microcytic hypochromic anemia was observed with high reticulocyte (40%) and ferritin (500 microg/L) levels, and hemoglobinopathy was suspected. No abnormal bands were visible on alkaline electrophoresis and high performance liquid chromatography (HPLC). The Hb A2 level was normal (2.7%) and the erythrocyte count was low (3.59 x 10(12)/L) with a normal haptoglobin level (68 mg/100 mL). None of the common alpha-thalassemia (thal) deletion defects were present. The beta-globin gene sequence was normal but the alpha2-globin gene sequence revealed an ATG-->ATA transition at codon 32, changing the methionine into an isoleucine residue. The mutation, called Hb Amsterdam, was observed in the mother of the proband, who was also heterozygous for the--alpha3.7-thal deletion and affected by a moderate microcytic hypochromic anemia. Both Hb Amsterdam and the--alpha(-3.7) allele were found in association with a new polymorphism, IVS-I-39 (C-->T), previously observed in our laboratory in seven patients of African origin, on both the alpha1 and alpha2 genes. In addition, Hb Amsterdam was also associated with the common African alpha2 polymorphism (G-->CTCGGCCC at position 7238 and T-->G at position 7174). Hb Amsterdam is the first mutation ever described at codon alpha32, a position involved in alpha1/beta1 interaction. The possibility of a contribution of this mutation to the nephropatic state of the proband is discussed.
authors.affiliation: The Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: Mark
authors.initials: M
authors.lastname: Vervloet
authors.forename: Sonja
authors.initials: S
authors.lastname: Zweegman
authors.forename: Peter
authors.initials: P
authors.lastname: van Delft
authors.forename: Nicole
authors.initials: N
authors.lastname: Akkermans
authors.forename: Sandra
authors.initials: S
authors.lastname: Arkestijn
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000349:Africa; D000747:Anemia, Hypochromic / Q000235:genetics; D044383:Black People / Q000235:genetics; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D017354:Point Mutation; D011110:Polymorphism, Genetic; D051437:Renal Insufficiency / Q000175:diagnosis / Q000628:therapy; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000208:ethnology / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; C508159:hemoglobin Amsterdam