Deletion and duplication of 15q24: molecular mechanisms and potential modification by additional copy number variants.
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.
El-Hattab
Ayman W
AW
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Zhang
Feng
F
Maxim
Rolanda
R
Christensen
Katherine M
KM
Ward
Jewell C
JC
Hines-Dowell
Stacy
S
Scaglia
Fernando
F
Lupski
James R
JR
Cheung
Sau Wai
SW
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