A deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene produces the phenotype of inclusion body beta-thalassemia.
Dominant inherited beta-thalassemias describe those beta-thalassemia variants that result in a thalassemia intermediate phenotype in individuals who have inherited only a single copy of the abnormal beta gene. This form of thalassemia is characterized by moderately severe anemia with jaundice and splenomegaly; it is also characterized by the presence of inclusion bodies in the red blood cell precursors and has, therefore, previously been referred to as inclusion body beta-thalassemia. We describe a case of inclusion body beta-thalassemia in a 51-year-old Spanish male caused by a deletion of 11 bp (CD 131-134) in exon 3 of the beta-globin gene. The deletion of 11 bp in exon 3 of the beta-globin chain is predicted to produce an anomalous chain of 134 amino acids instead of the normal 146 with an extremely altered amino acid sequence from residues 131-134. Although this shortened variant would lead to a missing H helix, which is involved in alpha1beta1 contact and alpha1beta2 subunit interactions, the variant chain can still be bound to the heme group and acquire a secondary structure that is not suitable for the formation of stable dimers or tetramers and also less susceptible to proteolytic degradation. This is the first report of such a beta-thalassemia mutation.
Servicio de Hematología y Hemoterapia, Hospital Clínico San Carlos, C/ Profesor Martín Lagos s/n, 28040, Madrid, Spain.
Paloma
P
Ropero
Ana
A
Villegas
Miguel
M
Martínez
Fernando
F
Ataulfo González Fernández
Celina
C
Benavente
Marta
M
Mateo
D004252:DNA Mutational Analysis; D005091:Exons; D016368:Frameshift Mutation; D005799:Genes, Dominant; D005914:Globins / Q000235:genetics*; D006418:Heme; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D010641:Phenotype; D017433:Protein Structure, Secondary; D017384:Sequence Deletion; D017086:beta-Thalassemia / Q000235:genetics* / Q000473:pathology
D006455:Hemoglobins, Abnormal; D006418:Heme; D005914:Globins; D010447:Peptide Hydrolases