title: Deletion and duplication of 15q24: molecular mechanisms and potential modification by additional copy number variants.
abstract: OBJECTIVE
  To investigate the potential influence of additional copy number variants in patients with 15q24 rearrangements and the possible underlying mechanisms for these rearrangements.
  
  
  METHODS
  Oligonucleotide-based chromosomal microarray analyses were performed, and the results were subsequently confirmed by fluorescence in situ hybridization analyses. Long-range polymerase chain reaction amplification and DNA sequencing analysis were used for breakpoint junction sequencing.
  
  
  RESULTS
  We describe a 15-year-old boy with cognitive impairment and dysmorphic features with deletions in 15q24 and 3q21, a 2-month-old female infant with growth deficiency, heterotaxy, cardiovascular malformations, intestinal atresia, and duplications in 15q24 and 16q22, and a 3.5-year-old boy with developmental delay, microcephaly, and dysmorphic features, with duplications in 15q24 and 2q36.3q37.1. Breakpoint sequencing for the 15q24 deletion in the first patient revealed microhomology and suggested the underlying mechanism of either nonhomologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication.
  
  
  CONCLUSIONS
  The three described patients with 15q24 rearrangements have copy number variants at other loci and exhibit additional clinical features with a more severe phenotype than that observed in previously reported patients with isolated 15q24 rearrangements, suggesting that the genomic mutational load may contribute to the phenotypic severity and variability in patients with 15q24 rearrangements.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Ayman W
authors.initials: AW
authors.lastname: El-Hattab
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Rolanda
authors.initials: R
authors.lastname: Maxim
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Christensen
authors.forename: Jewell C
authors.initials: JC
authors.lastname: Ward
authors.forename: Stacy
authors.initials: S
authors.lastname: Hines-Dowell
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D002872:Chromosome Deletion; D058674:Chromosome Duplication / Q000235:genetics*; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype