A novel α(0) -thalassemia deletion in a Greek patient with HbH disease and ß-thalassemia trait.
Eur J Haematol
; 88(4): 356-62, 2012 Apr.
Article
em En
| MEDLINE
| ID: mdl-22324317
ABSTRACT
OBJECTIVES:
To determine the molecular basis in a Greek child suspected of having HbH disease and ß-thalassemia trait.METHODS:
Standard hematology, Hb electrophoresis, and HPLC. Multiplex ligation-dependent probe amplification (MLPA), direct sequencing, and breakpoint characterization by NimbleGen fine-tiling array analysis.RESULTS:
The index patient showed a moderate microcytic hypochromic anemia with normal ZPP and elevated HbA(2) , indicative for ß-thalassemia trait. However, the moderate microcytic hypochromic anemia along with the observation of HbH inclusions in occasional red blood cells suggested a coexisting α-thalassemia. Molecular analysis indicated that the propositus inherited the ß(+) -thalassemia mutation IVS2-745 (c>g) and a novel α(0) -thalassemia deletion from the mother, and the common non-deletion α-thalassemia allele α(2) (-5nt)α from the father. The α(0) -thalassemia deletion, named -â-(BGS) , is approximately 131.6 kb in length. It removes the major regulatory elements along with the functional α-globin genes but leaves the theta-gene intact.CONCLUSIONS:
The compound interaction of a ß-thalassemia defect along with a single functional α-globin gene is quite rare. Although patients with HbH/ß-thal and simple HbH disease have comparable levels of Hb, the absence of free ß-globin chains and thus detectable non-functional HbH means that in HbH/ß-thal, the levels of functional Hb are higher, resulting in a better compensated functional anemia. Rare large deletions as the one described here remain undetected by gap-PCR in routine molecular screening. The introduction of MLPA as a diagnostic screening tool may improve laboratory diagnostics for these defects. The use of NimbleGen fine-tiling arrays may give additional information about the precise location of breakpoints.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Talassemia beta
/
Talassemia alfa
/
Alfa-Globinas
/
Globinas beta
Limite:
Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Eur J Haematol
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda