Abstract
Heterotaxia is an aetiologically heterogeneous condition caused by an abnormal left-right axis formation, resulting in reversed left-right polarity of one or more organ systems. In a patient with heterotaxia and a de novo reciprocal translocation t(6;18)(q21;q21), we found that the PA26 gene was disrupted by the 6q21 breakpoint. Northern blot analysis showed decreased expression of the PA26 gene in an Epstein-Barr virus-transformed cell line of this patient. During early embryogenesis of Xenopus, the orthologue of PA26, XPA26 is exclusively expressed in the notochord, a midline structure. This further supports a possible role of PA26 in human situs determination. Mutation analysis of human PA26 gene in 40 unrelated individuals with unexplained heterotaxia failed to identify mutations, indicating that PA26 mutations are not a frequent cause of heterotaxia in humans. Analysis of the PA26 gene structure resulted in the identification of a novel PA26-related gene family, which we have named the sestrin family, and which comprises three closely related genes in human and in mouse.
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Acknowledgements
We thank Reinhilde Thoelen for excellent technical assistance. K.D. is a senior clinical investigator and H.P. is a Research Assistant of the Fund for Scientific Research, Flanders, Belgium (FWO-Vlaanderen). This work was supported by grants from Inter-Universitary Attraction Poles (Belgian State) and the Belgian Foundation for Research in Pediatric Cardiology.
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Peeters, H., Debeer, P., Bairoch, A. et al. PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse. Hum Genet 112, 573–580 (2003). https://doi.org/10.1007/s00439-003-0917-5
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DOI: https://doi.org/10.1007/s00439-003-0917-5