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Updated: Aug 6, 2026
09:16
Array Comparative Genomic Hybridization (Array CGH) for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Copy Number Gains at 17p11.2 Sparing RAI1: A Shared Phenotype Pattern
Christopher M Grochowski1,2, Shruti Pande1, Parneet Kaur1
1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
American Journal of Medical Genetics. Part A
|July 17, 2026
Summary
Genomic rearrangements at the 17p11.2 locus, outside the RAI1 gene, are linked to neurodevelopmental delays. This study identifies new genetic factors contributing to these conditions.
Area of Science:
- Genetics
- Genomic Medicine
- Neuroscience
Background:
- The 17p11.2 locus is characterized by low copy repeats (LCRs) and repetitive elements, leading to genomic rearrangements like copy number variations.
- Nonallelic homologous recombination (NAHR) between LCRs causes Potocki-Lupski Syndrome (duplication) and Smith-Magenis Syndrome (deletion), both involving the RAI1 gene.
- Uncommon copy number gains at 17p11.2 not including RAI1 have been observed in individuals with neurodevelopmental delay (NDD).
Purpose of the Study:
- To investigate copy number gains at the 17p11.2 locus in individuals with NDD phenotypes, specifically those not encompassing the RAI1 gene.
- To characterize the genomic variations, understand the DNA rearrangement mechanisms, and analyze breakpoint junctions.
- To correlate observed genomic findings with neurodevelopmental phenotypes and identify potential novel disease-associated genes or pathways.
Main Methods:
- Ascertainment of 15 individuals from 11 families with copy number gains at 17p11.2 not including RAI1.
- High-resolution array comparative genomic hybridization (array CGH).
- Short-read whole-genome sequencing (sr-GS) and long-read genome sequencing (lr-GS) including Oxford Nanopore (ONT) and PacBio HiFi.
- Breakpoint junctional analysis and systematic phenotypic study.
Main Results:
- 15 individuals from 11 families presented with copy number gains at 17p11.2 not involving RAI1, exhibiting a spectrum of neurodevelopmental phenotypes including developmental delay, intellectual disability, and behavioral problems.
- Genomic variations included simple copy number gains (7), higher order amplifications (2), and complex genomic rearrangements (2).
- Inherited variants were identified in 4 out of 11 families. Phenotypes were systematically studied and correlated with genomic findings.
Conclusions:
- Genomic rearrangements at the 17p11.2 locus, independent of the RAI1 gene, can cause neurodevelopmental phenotypes.
- These findings highlight the potential for other genes or regulatory elements within or near this locus to contribute to NDD.
- Further investigation is warranted to dissect the genetic mechanisms and identify novel genes contributing to phenotypic variability and previously unrecognized disease pathways.
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