Asymptomatic homozygous deletional beta(0)-thalassemia in an African individual.
Homozygosity or compound heterozygosity for beta(0)-thalassemia mutations most commonly results in a transfusion-dependent thalassemia major phenotype. In this report, we describe a 55-year-old male, from Guinea-Bissau, that had been asymptomatic and never transfused until being admitted to hospital with anemia, fever, splenomegaly, and asthenia. Following hospital admission, HIV-2 and Mycobacterium tuberculosis infections were diagnosed, and biochemical and molecular studies revealed homozygosity for beta(0)-thalassemia. At the molecular level, this is the first description of homozygosity for the beta(0)-Black 1,393-bp deletion. In this case, the complete absence of beta-globin gene expression seems to be compensated by an unusually high fetal globin gene expression (Hb F 96%). Beta-globin haplotyping results were compatible with the propositus being homozygous for the Black 2 haplotype and for the absence of the XmnI polymorphism at -158 of (G)gamma-globin gene (-/-). Co-inheritance of genetic factors usually associated with high Hb F levels was not detected. Otherwise, the propositus is a heterozygote for the alpha-globin gene 3.7-kb deletion that is a beneficial modulating factor but not sufficient to explain this extremely mild phenotype. This unusual genotype/phenotype association is discussed in terms of the mechanisms underlying hemoglobin switching during development.
Faustino
Paula
P
Centro de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge (INSA), Lisboa, Portugal. paula.faustino@insa.min-saude.pt
Reis
Ana Batalha
AB
Feliciano
Helena
H
Ferrão
Lénia
L
Pereira
Patrícia
P
Picanço
Isabel
I
Miranda
Armandina
A
Seixas
Teresa
T
Romão
Luísa
L
Júnior
Esmeraldina Correia
EC
Lavinha
João
J
D000740:Anemia; D001247:Asthenia; D001803:Blood Transfusion; D005319:Fetal Hemoglobin / Q000032:analysis; D005334:Fever; D017353:Gene Deletion; D005914:Globins / Q000235:genetics; D006169:Guinea-Bissau / Q000208:ethnology; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis; D015498:HIV-2; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011174:Portugal; D013163:Splenomegaly; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications / Q000175:diagnosis*
D005914:Globins; D005319:Fetal Hemoglobin