Nonrecurrent 17p11.2p12 Rearrangement Events that Result in Two Concomitant Genomic Disorders: The @entity12344 - XXXX Contiguous Gene Duplication Syndrome.

@entity5108 @entity16 @entity12344 @entity305 @entity177 @entity2421 @entity33237 @entity717 @entity72436
UNASSIGNED: The genomic duplication associated with @entity72436 ( @entity72436 ) maps in close proximity to the duplication associated with @entity5108 ( @entity5108 ). @entity72436 is characterized by @entity2421 , @entity177 to thrive, reduced body weight, @entity717 , and autistic features. @entity5108 is a common autosomal dominant distal symmetric peripheral @entity305 . The key dosage-sensitive genes @entity33237 and @entity12344 are respectively associated with @entity72436 and @entity5108 . Recurrent duplications accounting for the majority of subjects with these conditions are mediated by nonallelic homologous recombination between distinct low-copy repeat (LCR) substrates. The LCRs flanking a contiguous genomic interval encompassing both @entity33237 and @entity12344 do not share extensive homology; thus, duplications encompassing both loci are rare and potentially generated by a different mutational mechanism. We characterized genomic rearrangements that simultaneously duplicate @entity12344 and @entity33237 , including nine potential complex genomic rearrangements, in 23 subjects by high-resolution array comparative genomic hybridization and breakpoint junction sequencing. Insertions and microhomologies were found at the breakpoint junctions, suggesting potential replicative mechanisms for rearrangement formation. At the breakpoint junctions of these nonrecurrent rearrangements, enrichment of repetitive DNA sequences was observed, indicating that they might predispose to genomic instability and rearrangement. Clinical evaluation revealed @entity72436 and @entity5108 phenotypes with a potential earlier onset of @entity16 . Moreover, additional clinical findings might be observed due to the extra duplicated material included in the rearrangements. Our genomic analysis suggests replicative mechanisms as a predominant mechanism underlying @entity12344 - @entity33237 contiguous gene duplications and provides further evidence supporting the role of complex genomic architecture in genomic instability.
