title: Hb Nijkerk: a new mutation at codons 138/139 of the beta-globin gene inducing severe hemolytic anemia in a Dutch girl.
abstract: We describe a new structural mutant of the beta-globin chain in a 17-year-old Dutch Caucasian girl. The mutant is associated with a severe pathology as a consequence of hyper-instability of the hemoglobin tetramer. The proband, whose parents had no history of hemolysis, was admitted to the hospital at 5 months of age with hemolytic anemia and splenomegaly. No indications for autoimmune defects or enzymopathies were found. Repeated hemoglobin electrophoresis on cellulose acetate revealed no abnormalities. At the age of 17 years, a minor abnormal band of less than 1% was detected on starch gel electrophoresis, migrating slightly faster than Hb A2. Sequencing of the beta-globin gene revealed heterozygosity for a 4 bp deletion (GCTA) in combination with a 1 bp insertion (T) at codons 138/139. This event eliminates two amino acids (Ala-Asn) and introduces a new residue (Tyr). We discuss the hematological and the pathophysiological consequences of this mutant, which is fully expressed as a gene product, and apparently assembled into unstable tetramers that precipitate shortly after.
authors.affiliation: Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: van den Berg
authors.forename: M C
authors.initials: MC
authors.lastname: Bruin
authors.forename: D
authors.initials: D
authors.lastname: Batelaan
authors.forename: P
authors.initials: P
authors.lastname: van Delft
authors.forename: R
authors.initials: R
authors.lastname: van Zwieten
authors.forename: D
authors.initials: D
authors.lastname: Roos
authors.forename: C L
authors.initials: CL
authors.lastname: Harteveld
authors.forename: L F
authors.initials: LF
authors.lastname: Bernini
authors.forename: P C
authors.initials: PC
authors.lastname: Giordano
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000743:Anemia, Hemolytic / Q000097:blood / Q000235:genetics*; D003062:Codon / Q000235:genetics; D005260:Female; D005914:Globins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009426:Netherlands
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; C119898:hemoglobin Nijkerk; D005914:Globins