@article{Sabina Swierczek_Archana M. Agarwal_Kubendran Naidoo_Felipe R. Lorenzo_Jonathan Whisenant_Roberto H. Nussenzveig_Neeraj Agarwal_Theresa L. Coetzer_Josef T. Prchal_2013, place={Pavia, Italy}, title={Novel exon 2 α spectrin mutation and intragenic crossover: three morphological phenotypes associated with four distinct α spectrin defects}, volume={98}, url={https://haematologica.org/article/view/6874}, DOI={10.3324/haematol.2013.086629}, abstractNote={Hereditary pyropoikilocytosis is a severe hemolytic anemia caused by spectrin deficiency and defective spectrin dimer self-association, typically found in African populations. We describe two Utah families of northern European ancestry including 2 propositi with atypical non-microcytic hereditary pyropoikilocytosis, 7 hereditary elliptocytosis members and one asymptomatic carrier. The underlying molecular defect is a novel mutation in the alpha(α) spectrin gene, <em>SPTA</em><sup>R34P</sup> that impairs spectrin tetramer formation. It is inherited <em>in trans</em> to the hypomorphic <em>SPTA</em><sup>αLELY</sup> in the 2 propositi and 5 of 7 hereditary elliptocytosis individuals indicating that <em>SPTA</em><sup>αLELY</sup> is not the sole determinant of the variable clinical expression. α Spectrin mRNA was mildly decreased in all hereditary elliptocytosis subjects, whereas both hereditary pyropoikilocytosis propositi had a severe decrease to ~10% of normal. Genotyping identified a unique <em>SPTA</em> intragenic crossover and uniparental disomy in one hereditary elliptocytosis individual. Two additional crossover events demonstrated the susceptibility of <em>SPTA</em> gene to rearrangement and revealed a novel segregation of the two <em>SPTA</em><sup>αLELY</sup> mutations. We conclude that the profound phenotypic heterogeneity in these families can be attributed to the <em>SPTA</em><sup>R34P</sup> mutation in combination with: 1) inheritance <em>in trans</em> of either <em>SPTA</em><sup>αLELY</sup>; or 2) the wild-type SPTA; 3) a decrease of α spectrin mRNA; and 4) <em>SPTA</em&gt; intragenic crossover.}, number={12}, journal={Haematologica}, author={Sabina Swierczek and Archana M. Agarwal and Kubendran Naidoo and Felipe R. Lorenzo and Jonathan Whisenant and Roberto H. Nussenzveig and Neeraj Agarwal and Theresa L. Coetzer and Josef T. Prchal}, year={2013}, month={Dec.}, pages={1972-1979} }