Abstract
Several hypotheses have been proposed to explain the phenotypic variability between parent and offspring carrying the same genomic imbalance, including unmasking of a recessive variant by a chromosomal deletion. Here, 19 patients with neurodevelopmental disorders harboring a rare deletion inherited from a healthy parent were investigated by whole-exome sequencing to search for SNV on the contralateral segment. This strategy allowed us to identify a candidate variant in two patients in the NUP214 and NCOR1 genes. This result demonstrates that the analysis of the genes included in non-deleted contralateral allele is a key point in the etiological investigation of patients harboring a deletion inherited from a parent. Finally, this strategy is also an interesting approach to identify new recessive intellectual disability genes.
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Acknowledgements
Funding for the project was provided by the “National Research Agency” (ANR-10-IAHU-01), the “Fondation pour la Recherche Médicale” (DEQ20160334938) and the “Fondation Maladies Rares”.
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Egloff, M., Nguyen, LS., Siquier-Pernet, K. et al. Whole-exome sequence analysis highlights the role of unmasked recessive mutations in copy number variants with incomplete penetrance. Eur J Hum Genet 26, 912–918 (2018). https://doi.org/10.1038/s41431-018-0124-4
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DOI: https://doi.org/10.1038/s41431-018-0124-4
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