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Updated: May 16, 2026
Array Comparative Genomic Hybridization (Array CGH) for Detection of Genomic Copy Number Variants
Published on: February 21, 2015
Copy number variation in pediatric multiple sclerosis
J P McElroy1, L B Krupp, B A Johnson
1Department of Neurology, University of California at San Francisco, USA. Joseph.McElroy@OSUMC.edu
Insights
This study investigated copy number variations (CNVs) in pediatric multiple sclerosis (MS) patients. While no direct cause was found, a rare CNV linked to ARSACS disease was identified, aiding diagnosis and prognosis.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Pediatric multiple sclerosis (MS) comprises 2-4% of all MS cases.
- The underlying pathophysiology of pediatric MS versus adult MS remains unclear.
- Copy number variations (CNVs) are hypothesized to cause extreme early-onset diseases due to their potential to affect multiple genes.
Observation:
- Comparative genomic hybridization (CGH) was used to analyze 30 pediatric MS patients and their parents.
- The study focused on identifying de novo CNVs, which are newly occurred genetic variations.
- Agilent 1M CGH array was employed for high-resolution analysis.
Findings:
- Ten novel CNVs, not previously reported in the Database of Genomic Variants (DGV), were identified.
- Fifty-five putatively de novo CNVs were found, with most being common in the DGV.
- One rare, private CNV was discovered, encompassing the SACS gene, associated with autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
Implications:
- This is the first study to analyze CNVs in pediatric MS.
- The identified SACS gene CNV led to the diagnosis of ARSACS-like disease alongside MS in one patient.
- The findings improve understanding of disease course and prognosis in complex pediatric neurological cases.
Background:
Pediatric onset multiple sclerosis (MS) accounts for 2-4% of all MS. It is unknown whether the disease shares the same underlying pathophysiology found in adult patients or an extreme early onset phenotype triggered by distinct biological mechanisms. It has been hypothesized that copy number variations (CNVs) may result in extreme early onset diseases because CNVs can have major effects on many genes in large genomic regions.
Objectives And Methods:
The objective of the current research was to identify CNVs, with a specific focus on de novo CNVs, potentially causing early onset MS by competitively hybridizing 30 white non-Hispanic pediatric MS patients with each of their parents via comparative genomic hybridization (CGH) analysis on the Agilent 1M CGH array.
Results And Discussion:
We identified 10 CNVs not overlapping with any CNV regions currently reported in the Database of Genomic Variants (DGV). Fifty-five putatively de novo CNVs were also identified: all but one common in the DGV. We found the single rare CNV was a private variation harboring the SACS gene. SACS mutations cause autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) disease. Additional clinical review revealed that the patient with the SACS gene CNV shared some features of both MS and ARSACS.
Conclusions:
This is the first reported study analyzing pediatric MS CNVs. While not yielding causal variation in our initial pediatric dataset, our approach confirmed diagnosis of an ARSACS-like disease in addition to MS in the affected individual, which led to a more complete understanding of the patient's disease course and prognosis.
Related Concept Videos
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:05Single Nucleotide Polymorphisms-SNPs
01:19Multiple Sclerosis l: Introduction