Alpha-thalassemia phenotype induced by the new IVS-II-2 (T --> A) splice donor site mutation on the alpha2-globin gene.
We present a family of North European extraction referred for a refractory non iron depleted microcytic anemia. The proband, a 36 year-old male, presented with chronic borderline anemia and microcytic hypochromic parameters. No abnormal hemoglobin (Hb) fractions were observed on high performance liquid chromatography (HPLC) or on alkaline electrophoresis. Gap-polymerase chain reaction (gap-PCR) excluded the seven common alpha-thalassemia (thal) deletion defects. However, the beta/alpha-globin chain synthesis ratio measured in vitro was unbalanced, indicating a reduced expression of the alpha-globin genes. Direct sequencing of the alpha-globin genes revealed heterozygosity for a T --> A transversion at the IVS-II-2 position of the alpha2 gene. This is the first IVS-II splice donor site mutation described on the alpha2-globin gene.
Harteveld
Cornelis L
CL
Department of Human and Clinical Genetics, The Hemoglobinopathies Laboratory, Leiden University Medical Center, Leiden, The Netherlands.
Jebbink
Max C W
MC
van der Lely
Nico
N
van Delft
Peter
P
Akkermans
Nicole
N
Arkesteyn
Sandra
S
Giordano
Piero C
PC
D000328:Adult; D000483:Alleles; D017398:Alternative Splicing; D000747:Anemia, Hypochromic / Q000097:blood / Q000235:genetics*; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D005192:Family Health; D017353:Gene Deletion; D005914:Globins / Q000235:genetics*; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D021122:Protein Subunits / Q000235:genetics; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics*
D006454:Hemoglobins; D021122:Protein Subunits; D005914:Globins