Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion

摘要: Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder characterized by growth retardation, intellectual disability, upper limb abnormalities, hirsutism, and characteristic facial features. In this study we explored the occurrence of intragenic NIPBL copy number variations (CNVs) in cohort 510 sequence-negative patients with suspected CdLS. Copy analysis was performed custom exon-targeted oligonucleotide array-comparative genomic hybridization and/or MLPA. Whole-genome SNP array used to further characterize rearrangements extending beyond gene. We identified CNVs 13 (2.5%) including one duplication deletion mosaic state. Breakpoint sequences two provided evidence microhomology-mediated replicative mechanism as potential predominant contributor NIPBL. Patients for whom clinical information available share classical CdLS features craniofacial defects. Our experience studying frequency NIBPL largest series date widens mutational spectrum emphasizes utility performing deletion/duplication