An alpha-thalassemia phenotype in a Dutch Hindustani, caused by a new point mutation that creates an alternative splice donor site in the first exon of the alpha2-globin gene.
The proband is an elderly woman (79 years of age) of Surinamese-Hindustani origin, suspected of being a carrier of a nondeletional alpha-thalassemia (thal) because of a moderate microcytic hypochromic anemia at normal ferritin levels and in the absence of any other alpha-thal deletions. Sequence analysis revealed a silent mutation (GGC-->GGT) at codon 22 of the alpha2-globin gene. This mutation generates a splice donor site consensus sequence (GGTGAG) between codons 22 and 23. The abnormally spliced mRNA leads to a premature termination between codons 48 and 49. The presence of a downstream intron may induce the intracellular degradation of the affected mRNA, a pathway known as nonsense mediated decay (NMD), and this explains the alpha(+)-thal phenotype observed in the patient. The codon 22 (GGC-->GGT) transition described in this report is the first mutation creating a splice donor site in one of the alpha-globin genes.
Harteveld
Cornelis L
CL
Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. C.L.Harteveld@lumc.nl
Wijermans
Pierre W
PW
van Delft
Peter
P
Rasp
Ellen
E
Haak
Hans L
HL
Giordano
Piero C
PC
D000368:Aged; D000747:Anemia, Hypochromic / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics*; D005260:Female; D006801:Humans; D010443:Peptide Chain Termination, Translational / Q000235:genetics; D017354:Point Mutation; D012326:RNA Splicing / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics*
D018388:Codon, Terminator