title: Alternative outcomes of pathogenic complex somatic structural variations in the genomes of NF1 and NF2 patients.
abstract: Multiplex ligation-dependent probe amplification (MLPA) has been widely used to identify copy-number variations (CNVs), but MLPA's sensitivity and specificity in mosaic CNV detection are largely unknown. Here, we present two mosaic deletions identified by MLPA as NF1 deletion of exons 17-21 and NF2 deletion of exons 9-10. Through cDNA analysis, genomic breakpoint-spanning PCR and Sanger sequencing, we found however both NF1 and NF2 deletions are each composed of two consecutive deletions, which cannot be differentiated by MLPA. Importantly, these consecutive deletions are most likely originating from a single genomic rearrangement and have been preserved independently in different populations of cells.
authors.affiliation: Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Meng-Chang
authors.initials: MC
authors.lastname: Hsiao
authors.affiliation: Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.|Medical University of Gdansk, Gdansk, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Piotrowski
authors.affiliation: Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Andrzej Brunon
authors.initials: AB
authors.lastname: Poplawski
authors.affiliation: Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Callens
authors.affiliation: Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Chuanhua
authors.initials: C
authors.lastname: Fu
authors.affiliation: Medical Genomics Laboratory, Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. lmessiaen@uabmc.edu.
authors.forename: Ludwine
authors.initials: L
authors.lastname: Messiaen
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D017353:Gene Deletion; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D009154:Mutation / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000235:genetics*; D016518:Neurofibromatosis 2 / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods
keywords: Deletion; MLPA; Mosaic rearrangement mechanism; NF1; NF2