Homozygosity for nondeletion delta-beta(0) thalassemia resulting in a silent clinical phenotype.
The clinical phenotype of homozygous beta thalassemia varies in severity from the mild thalassemia intermedia to the severe thalassemia major. This variability depends largely on the molecular heterogeneity of beta thalassemia defects. We report the first case of a homozygous state for nondeletion Sardinian delta-beta(0) thalassemia, which resulted in a symptomless clinical phenotype with a peculiar hemoglobin (Hb) pattern (99.8% Hb F and 0.2% Hb A(2)). The molecular defect was characterized by the presence of 2 nucleotide substitutions: -196C>T in the promoter of the Agamma-globin gene and beta 39C>T nonsense mutation. The absence of typical beta thalassemia clinical findings was due to the high Hb F output, which compensated for the absence of beta chains. The near absence of Hb A(2) may have resulted from either alterations in the globin gene transcriptional complex with preferential activation of gamma-globin genes and suppression of delta-globin genes or preferential survival of red blood cells with the highest Hb F content and low Hb A(2) level.
Galanello
Renzo
R
Ospedale Regionale Microcitemie; and Dipartimento di Scienze Biomediche e Biotecnologie and Dipartimento di Scienze Pediatriche, Università di Cagliari, Italy. renzo.galanello@mcweb.unica.it
Barella
Susanna
S
Satta
Stefania
S
Maccioni
Liliana
L
Pintor
Carlo
C
Cao
Antonio
A
D005260:Female; D005914:Globins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D005810:Multigene Family; D009154:Mutation; D017384:Sequence Deletion; D017086:beta-Thalassemia / Q000235:genetics* / Q000503:physiopathology
D005914:Globins