MISSED BY OTHERS, DETECTED BY US
Genomic Unity® Case Study

Single exon PEX1 deletion confirms suspected Zellweger spectrum disorder diagnosis

Clinical presentation

A 2-year-old female with a suspected Zellweger spectrum disorder clinical diagnosis presented with the following symptoms:

  • Neurodevelopmental delay
  • Bilateral sensorineural hearing loss
  • Vertical nystagmus
  • Ventricular septal defect
  • Impaired liver function
  • Gastrointestinal reflux
  • Ataxic gait

Previous genetic testing

Multiple tests were performed with negative results, including exome testing that identified a pathogenic splicing variant in the recessive PEX1 gene, but no second variant. Targeted PEX1 del/dup testing also didn’t identify a second variant:

  • Chromosomal microarray
  • Whole exome sequencing
  • PEX1 del/dup analysis
  • Mitochondrial genome sequencing

Genomic Unity® Testing

was ordered because of its ability to identify all major variant types in a single test.

Results and interpretation

Variantyx Genomic Unity® testing identified a maternally inherited, pathogenic 4.86 kb PEX1  deletion together with the previously identified, paternally inherited, PEX1 splicing variant.

The deletion removes the final exon and is expected to result in loss of protein function.

Diagnosis: Zellweger spectrum disorder

IGV view of PEX1 variants

Uniform data from WGS clearly shows both the splicing (left) and single exon deletion (right) variants.

The Variantyx Difference

Why was Genomic Unity® testing able to identify the single exon deletion missed by exome and targeted del/dup testing?

  • Exomes are typically unable to detect deletions less than 3 exons in size.

  • Even targeted del/dup analysis may miss single exon deletions.
    Variantyx genome analysis has a detection range from 1 bp to whole chromosomal events. It easily detected this single exon deletion while simultaneously ruling out an intronic variant originally suspected by the clinician due to the negative PEX1 del/dup analysis.

  • One breakpoint occurs in intron 23 while the second breakpoint occurs in the intergenic region downstream of the PEX1 gene, adding to the complexity of detection.
    Variantyx genome analysis includes all intronic, regulatory and intergenic regions, enabling breakpoint detection regardless of location.

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