Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion. Issue 2 (14th November 2013)

• Record Type: Journal Article
• Authors: Cheng, Yu‐Wei; Tan, Christopher A.; Minor, Agata; Arndt, Kelly; Wysinger, Latrice; Grange, Dorothy K.; Kozel, Beth A.; Robin, Nathaniel H.; Waggoner, Darrel; Fitzpatrick, Carrie; Das, Soma; Gaudio, Daniela del
• Is Part Of: Molecular genetics & genomic medicine. Volume 2:Issue 2(2014:Mar.)
• Page Start: 115
• Page End: 123
• Publication Date: 2013-11-14
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.48
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg348-abs-0001"> <title>Abstract</title> <p>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 <italic>NIPBL</italic> copy number variations (CNVs) in a cohort of 510 <italic>NIPBL</italic> sequence‐negative patients with suspected CdLS. Copy number analysis was performed by custom exon‐targeted oligonucleotide array‐comparative genomic hybridization and/or MLPA. Whole‐genome SNP array was used to further characterize rearrangements extending beyond the <italic>NIPBL</italic> gene. We identified <italic>NIPBL</italic> CNVs in 13 patients (2.5%) including one intragenic duplication and a deletion in mosaic state. Breakpoint sequences in two patients provided further evidence of a microhomology‐mediated replicative mechanism as a potential predominant contributor to CNVs in <italic>NIPBL</italic>. Patients for whom clinical information was available share classical CdLS features including craniofacial and limb defects. Our experience in studying the frequency of <italic>NIBPL</italic> CNVs in the largest series of patients to date widens the mutational spectrum of <italic>NIPBL</italic> and emphasizes the clinical utility of performing <italic>NIPBL</italic> deletion/duplication analysis in patients with CdLS.</p> </abstract>