In a recent publication in the American Journal of Medical Genetics, our team demonstrated the power of combining optical genome mapping (OGM) with whole genome sequencing to solve complex diagnostic cases. This case study highlights why comprehensive genomic analysis is becoming the standard of care for patients with unexplained developmental disorders.
The Challenge: When Standard Testing Falls Short
A male patient presented with a multisystem developmental disorder, exhibiting multiple clinical features that suggested a genetic cause. Traditional chromosomal microarray analysis and standard genetic testing failed to identify the underlying cause, leaving the family without answers.
The Discovery: A Complex Chromosomal Puzzle
By employing optical genome mapping alongside whole genome sequencing, our team identified a previously undetected complex chromosomal rearrangement:
- A subtelomeric deletion at Xq28 (the tip of the X chromosome)
- An inserted duplication from chromosome 7p22.3
- A complex structural variant involving multiple genomic regions
Why This Matters: The Power of Multi-Platform Diagnostics
This case exemplifies several critical advantages of our integrated diagnostic approach:
Detection of Balanced Rearrangements:
Optical genome mapping excels at identifying balanced chromosomal rearrangements and complex structural variants that are invisible to microarray technology and difficult to detect with short-read sequencing alone.
Comprehensive Structural Variant Analysis:
While whole genome sequencing provides nucleotide-level resolution, OGM offers a complementary long-range view of chromosomal architecture, detecting structural changes spanning hundreds of kilobases.
Clinical Impact:
Identifying these complex rearrangements provides families with a definitive molecular diagnosis, enabling accurate genetic counseling, recurrence risk assessment, and in some cases, targeted therapeutic interventions.
The Future of Diagnostic Genomics
This publication adds to growing evidence that combining multiple genomic technologies increases diagnostic yield significantly. At Praxis Genomics, we routinely employ this multi-platform approach because single technologies, no matter how sophisticated, cannot capture the full spectrum of genetic variation.
Read the full publication: American Journal of Medical Genetics Part A
