Blood, 1 September 2002, Vol. 100, No. 5, pp. 1913-1914
BRIEF REPORT
Homozygosity for nondeletion 
-
0 thalassemia
resulting in a silent clinical phenotype
Renzo Galanello,
Susanna Barella,
Stefania Satta,
Liliana Maccioni,
Carlo Pintor, and
Antonio Cao
From the Ospedale Regionale Microcitemie; and
Dipartimento di Scienze Biomediche e Biotecnologie and Dipartimento di
Scienze Pediatriche, Università di Cagliari, Cagliari, Italy.
The clinical phenotype of homozygous 
thalassemia varies in
severity from the mild thalassemia intermedia to the severe thalassemia major. This variability depends largely on the molecular heterogeneity of thalassemia defects. We report the first case of a homozygous state for nondeletion Sardinian 
-0 thalassemia, which
resulted in a symptomless clinical phenotype with a peculiar hemoglobin
(Hb) pattern (99.8% Hb F and 0.2% Hb A2). The molecular
defect was characterized by the presence of 2 nucleotide substitutions:
196C>T in the promoter of the A
-globin gene and 39C>T
nonsense mutation. The absence of typical thalassemia clinical
findings was due to the high Hb F output, which compensated for the
absence of chains. The near absence of Hb A2 may have resulted from either alterations in the globin gene transcriptional complex with preferential activation of -globin genes and
suppression of -globin genes or preferential survival of red blood
cells with the highest Hb F content and low Hb A2 level.
