Abstract
Genomic rearrangements are an increasingly recognized mechanism of human phenotypic variation and susceptibility to disease. Sotos syndrome is characterized by overgrowth, macrocephaly, developmental delay and advanced osseous maturation. Haploinsufficiency of NSD1, caused by inactivating point mutations or deletion copy number variants, is the only known cause of Sotos syndrome. A recurrent 2 Mb deletion has been described with variable frequency in different populations. In this study, we report two individuals of different ethnic and geographical backgrounds, with duplications reciprocal to the common Sotos syndrome deletion. Our findings provide evidence for the existence of a novel syndrome of short stature, microcephaly, delayed bone development, speech delay and mild or absent facial dysmorphism. The phenotype is remarkably opposite to that of Sotos syndrome, suggesting a role for NSD1 in the regulation of somatic growth in humans.
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Acknowledgements
We thank our patients and their families for their cooperation. This work was made possible in part by grants from the IWT (SBO-60848) and GOA/2006/12, and from the SymBioSys Center of Excellence (Research Council, KU Leuven, EF/05/007) to JRV, and by grant R13-0005-04/2008 from the Polish Ministry of Science and Higher Education to PS.
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Franco, L., de Ravel, T., Graham, B. et al. A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion. Eur J Hum Genet 18, 258–261 (2010). https://doi.org/10.1038/ejhg.2009.164
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DOI: https://doi.org/10.1038/ejhg.2009.164
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