A syndrome of short stature, microcephaly and speech delay is associated with duplications reciprocal to the common Sotos syndrome deletion |
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| Authors: | Luis M Franco Thomy de Ravel Brett H Graham Stephanie M Frenkel Jozef Van Driessche Pawel Stankiewicz James R Lupski Joris R Vermeesch Sau Wai Cheung |
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| Affiliation: | 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;2Centre for Human Genetics, Universitaire Ziekenhuizen Leuven, Leuven, Belgium;3Texas Children''s Hospital, Houston, TX, USA;4VZW Martine Van Camp, Diest, Belgium;5Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland;6Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA |
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| 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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| Keywords: | array comparative genomic hybridization Sotos syndrome microcephaly microduplication genomic disorders |
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