1. Whole-exome sequence analysis highlights the role of unmasked recessive mutations in copy number variants with incomplete penetrance
- Author
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Matthieu Egloff, Karine Siquier-Pernet, Lam-Son Nguyen, Geneviève Baujat, Valérie Malan, Patrick Nitschke, Christine Bole-Feysot, Valérie Cormier-Daire, Michel Vekemans, Laurence Colleaux, Tania Attié-Bitach, Université Paris Descartes - Paris 5 (UPD5), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Plateforme Bioinformatique [SFR Necker] (BIP-D), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,Male ,Penetrance ,medicine.disease_cause ,MESH: Penetrance ,MESH: Child ,MESH: Nuclear Receptor Co-Repressor 1 ,Exome ,Copy-number variation ,Child ,Genetics (clinical) ,Exome sequencing ,Genetics ,Mutation ,MESH: Exome ,MESH: Infant ,MESH: Young Adult ,Child, Preschool ,Female ,MESH: DNA Copy Number Variations ,Adult ,MESH: Mutation ,Adolescent ,DNA Copy Number Variations ,Genes, Recessive ,Biology ,Brief Communication ,03 medical and health sciences ,Young Adult ,MESH: Whole Exome Sequencing ,Exome Sequencing ,medicine ,Humans ,Nuclear Receptor Co-Repressor 1 ,Allele ,Gene ,Chromosomal Deletion ,Alleles ,MESH: Genes, Recessive ,MESH: Neurodevelopmental Disorders ,MESH: Adolescent ,MESH: Humans ,MESH: Alleles ,MESH: Child, Preschool ,Infant ,MESH: Adult ,MESH: Male ,Nuclear Pore Complex Proteins ,030104 developmental biology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Neurodevelopmental Disorders ,MESH: Female ,MESH: Nuclear Pore Complex Proteins - Abstract
International audience; 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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- 1970