title: Codon 24 (TAT>TAG) and codon 32 (ATG>AGG) (Hb Rotterdam): two novel alpha2 gene mutations associated with mild alpha-thalassemia found in the same family after newborn screening.
abstract: We report two novel alpha2-globin gene mutations found in the same Surinamese family. The proband, a newborn presenting during neonatal screening with 21.3% Hb Bart's (gamma4), proved to be a carrier of the common -alpha(3.7) deletion and a novel codon 32 (ATG>AGG) transversion that we named Hb Rotterdam. The father carried the same point mutation with borderline hemoglobin (Hb), MCV and low MCH values. The mother presented with a significant microcytic hypochromic anemia and also carried the -alpha(3.7) deletion and a second novel TAT>TAG transversion generating a stop codon at position 24. Shortly thereafter, Hb Rotterdam was again found in two unrelated adult females and in a Canadian newborn, all of African origin, suggesting that Hb Rotterdam could be a frequently occurring alpha(T) determinant in the Black population. Screening and characterization of the mutations, phenotype/genotype correlation and the issue of reporting newborn carriers of alpha-thalassemia (alpha-thal) are discussed.
authors.affiliation: Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. p.c.giordano@lumc.nl
authors.forename: Piero C
authors.initials: PC
authors.lastname: Giordano
authors.forename: Marjon H
authors.initials: MH
authors.lastname: Cnossen
authors.forename: Annemarie M S
authors.initials: AM
authors.lastname: Joosten
authors.forename: Cees A M
authors.initials: CA
authors.lastname: Jansen
authors.forename: Tineke E
authors.initials: TE
authors.lastname: Hakvoort
authors.forename: Margreet
authors.initials: M
authors.lastname: Bakker-Verweij
authors.forename: Sandra G J
authors.initials: SG
authors.lastname: Arkesteijn
authors.forename: Peter
authors.initials: P
authors.lastname: van Delft
authors.forename: John S
authors.initials: JS
authors.lastname: Waye
authors.forename: Marelle J
authors.initials: MJ
authors.lastname: Bouva
authors.forename: Cornelis L
authors.initials: CL
authors.lastname: Harteveld
mesh_terms: D000328:Adult; D003062:Codon / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008875:Middle Aged; D009154:Mutation; D015997:Neonatal Screening; D010375:Pedigree; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D003062:Codon; D006455:Hemoglobins, Abnormal; D055542:alpha-Globins