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

Homozygous, single-exon deletion and SNV variants provide two independent diagnoses

Clinical presentation

A 15-year-old male of consanguineous parents presented with clinical suspicion of a progressive neuromuscular disorder, plus the following symptoms:

  • Chronic respiratory disease
  • Chronic nocturnal hypoventilation
  • Hypoxemia
  • Ophthalmoplegia

Previous genetic testing

Testing was performed with non-diagnostic results. Including exome testing that identified a likely pathogenic SNV in the OPA1 gene, explaining only the ophthalmoplegia symptom.

  • Whole exome 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 homozygous, pathogenic, 2.77 kb single exon deletion in the COLQ gene together with a homozygous, likely pathogenic SNV in the CFTR gene – providing two independent molecular diagnoses.

The likely pathogenic SNV in the OPA1 gene was also identified.

Diagnosis: Congenital myasthenic syndrome 5, Cystic fibrosis, Optic atrophy

IGV view of COLQ and CFTR variants

Uniform data from WGS clearly shows both the 2.77 kb COLQ deletion (left) and CFTR SNV variant (right) inherited from both parents. The maternally inherited OPA1  SNV is not shown.

The Variantyx Difference

Why were these variants detected by Genomic Unity® testing, and not detected by exome testing?

  • Exomes are typically unable to detect deletions smaller than 3 exons in size.
    Variantyx genome analysis has a detection range from 1 bp to whole chromosomal events, easily detecting this single-exon COLQ deletion.

  • Both COLQ deletion breakpoints are intronic, adding to the complexity of detection.
    Variantyx genome analysis includes intronic regions, enabling breakpoint detection regardless of location.

  • While small sequence changes are usually detectable by exome testing, this CFTR variant is located near an exon/intron boundary that may have impacted probe coverage and ultimately read coverage.
    Variantyx genome sequencing does not use PCR amplification. Its uniform coverage across the entire gene, including at exon/intron boundaries, makes it easy to identify this exonic single nucleotide change.

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