Τίτλος:
A novel α 0-thalassemia deletion in a Greek patient with HbH disease and β-thalassemia trait
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: To determine the molecular basis in a Greek child suspected of having HbH disease and β-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 β-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 β +-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 -- BGS, is approximately 131.6kb 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 β-thalassemia defect along with a single functional α-globin gene is quite rare. Although patients with HbH/β-thal and simple HbH disease have comparable levels of Hb, the absence of free β-globin chains and thus detectable non-functional HbH means that in HbH/β-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. © 2011 John Wiley & Sons A/S.
Συγγραφείς:
Phylipsen, M.
Traeger-Synodinos, J.
van der Kraan, M.
van Delft, P.
Bakker, G.
Geerts, M.
Kanavakis, E.
Stamoulakatou, A.
Karagiorga, M.
Giordano, P.C.
Harteveld, C.L.
Περιοδικό:
European Journal of Haematology
Λέξεις-κλειδιά:
alpha globin; hemoglobin H, allele; alpha thalassemia; article; beta thalassemia; child; comparative genomic hybridization; disease association; electrophoresis; erythrocyte; female; gene deletion; gene mutation; Greece; high performance liquid chromatography; human; human cell; iron deficiency anemia; male; multiplex ligation dependent probe amplification; polymerase chain reaction; preschool child; priority journal, Alleles; alpha-Globins; alpha-Thalassemia; beta-Globins; beta-Thalassemia; Child, Preschool; Chromatography, High Pressure Liquid; Comparative Genomic Hybridization; Family Health; Female; Gene Deletion; Greece; Humans; Male; Sequence Analysis, DNA
DOI:
10.1111/j.1600-0609.2012.01748.x
