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Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome

Abstract

Next-generation RNA sequence analysis of platelets from an individual with autosomal recessive gray platelet syndrome (GPS, MIM139090) detected abnormal transcript reads, including intron retention, mapping to NBEAL2 (encoding neurobeachin-like 2). Genomic DNA sequencing confirmed mutations in NBEAL2 as the genetic cause of GPS. NBEAL2 encodes a protein containing a BEACH domain that is predicted to be involved in vesicular trafficking and may be critical for the development of platelet α-granules.

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Figure 1: Abnormal sequence reads in NBEAL2 transcripts observed in platelet RNA from an individual with GPS.
Figure 2: Mutation analysis of NBEAL2.

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Acknowledgements

We thank the families that participated in this study. This work was supported by grants from the US National Institutes of Health (NIH) to J.D.P. (NIH HL084086-01), A.S.W. (NIH HL066277 and HL091283), J.W.R. (NIH T32 HL105321), B.C.S. and G.-Y.R. (NIH UL1RR024979), the Canadian Institutes of Health Research to W.H.A.K. (MOP-81208), J.P. and N.B.L. (MOP-84556), and the American Heart Association to H.S. (AHA 09BG1A2250381). We thank R. Wong from the Diabetes and Endocrinology Research Center Molecular Biology Core at the University of Colorado–Denver for sequencing assistance (grant NIH P30DK57516), the Bioinformatics and Molecular Evolution Group, Dublin City University for the use of their computational facilities and D. Lim for preparing figures.

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Authors

Contributions

Designed experiments: W.H.A.K., A.S.W., J.H. and J.D.P. Performed research, analyzed data: W.H.A.K., A.S.W., J.D.P., J.H., L.L., H.S., H.C., J.W.R., F.G.P., D.U., S.F., B.N., R.G., M.S., K.W., G.-Y.R., S.M.J., B.C.S., J.M., N.B.L. and J.P. Wrote and edited manuscript: W.H.A.K., A.S.W., J.D.P., J.P., N.B.L., J.H., J.W.R. and F.G.P.

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Correspondence to Walter HA Kahr or Jorge Di Paola.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Table 1 and Supplementary Figures 1–6 (PDF 2249 kb)

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Kahr, W., Hinckley, J., Li, L. et al. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nat Genet 43, 738–740 (2011). https://doi.org/10.1038/ng.884

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