A novel alpha(0)-thalassemia deletion in a Greek patient with HbH disease and beta-thalassemia trait

作者:Phylipsen Marion; Traeger Synodinos Jan; van der Kraan Martijn; van Delft Peter; Bakker Greet; Geerts Mariska; Kanavakis Emmanuel; Stamoulakatou Alexandra; Karagiorga Markissia; Giordano Piero C; Harteveld Cornelis L*
来源:European Journal of Haematology, 2012, 88(4): 356-362.
DOI:10.1111/j.1600-0609.2012.01748.x

摘要

Objectives: To determine the molecular basis in a Greek child suspected of having HbH disease and beta-thalassemia trait. Methods: Standard hematology, Hb electrophoresis, and HPLC. Multiplex ligationdependent 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 HbA2, indicative for b- thalassemia trait. However, the moderate microcytic hypochromic anemia along with the observation of HbH inclusions in occasional red blood cells suggested a coexisting a- thalassemia. Molecular analysis indicated that the propositus inherited the b +- thalassemia mutation IVS2- 745 (c%26gt; g) and a novel a 0 - thalassemia deletion from the mother, and the common non- deletion a- thalassemia allele a2(- 5nt) a from the father. The a 0 - thalassemia deletion, named - - BGS, is approximately 131.6 kb in length. It removes the major regulatory elements along with the functional a- globin genes but leaves the theta- gene intact. Conclusions: The compound interaction of a b- thalassemia defect along with a single functional a- globin gene is quite rare. Although patients with HbH/ b- thal and simple HbH disease have comparable levels of Hb, the absence of free b- globin chains and thus detectable non- functional HbH means that in HbH/ b- 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.

  • 出版日期2012-4