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.
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.
Giordano
Piero C
PC
Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. p.c.giordano@lumc.nl
Cnossen
Marjon H
MH
Joosten
Annemarie M S
AM
Jansen
Cees A M
CA
Hakvoort
Tineke E
TE
Bakker-Verweij
Margreet
M
Arkesteijn
Sandra G J
SG
van Delft
Peter
P
Waye
John S
JS
Bouva
Marelle J
MJ
Harteveld
Cornelis L
CL
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*
D003062:Codon; D006455:Hemoglobins, Abnormal; D055542:alpha-Globins