alpha-thalassaemia masked by beta gene defects and a new polyadenylation site mutation on the alpha2-globin gene.
We report three examples of chronic anaemia involving complex combinations of alpha- and beta-globin gene defects. The first case had a potential Hb H disease caused by the classic SEA/RW deletions masked by Hb E [beta26(B8)Glu-->Lys] in the homozygous state. The second had an unusual Hb H disease caused by compound heterozygosity for two different alpha2 polyadenylation site mutations masked by a beta-thalassaemia heterozygosity. The third had an intermediate alpha-thalassaemia with considerable anaemia caused by an as yet unknown polyadenylation site (AATAAA>AATAAC) mutation in combination with a common RW deletion masked by a common Hb C [beta6(A3)Glu-->Lys] heterozygosity. Diagnostic methods, genotype/phenotype correlations and the chance of overlooking these combinations during risk assessment in a multiethnic society are discussed.
Harteveld
Cornelis L
CL
The Reference Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics (LDGA), Leiden University Medical Center, Leiden.
Oosterhuis
Wytze P
WP
Schoenmakers
Christian H H
CH
Ananta
Hardjawardhama
H
Kos
Snjezana
S
Bakker Verweij
Margaretha
M
van Delft
Peter
P
Arkesteijn
Sandra G J
SG
Phylipsen
Marion
M
Giordano
Piero C
PC
D000328:Adult; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D039104:RNA 3' Polyadenylation Signals / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics
D006455:Hemoglobins, Abnormal; D055542:alpha-Globins; D055544:beta-Globins