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

Inversion explains developmental delay and physical anomalies

Clinical presentation

An 11-year-old male suspected of having Angelman syndrome presented with a history of global developmental delay and multiple clinical symptoms including:

  • Absent speech
  • Autism spectrum disorder, behavioral abnormalities
  • Restrictive lung disease
  • Dental anomalies
  • Hypotonia
  • Abnormal gait
  • Astigmatism
  • Megameatus

Previous genetic testing

Multiple tests were performed with negative results including:

  • Chromosomal microarray
  • FMR1  testing
  • UBE3A sequencing and methylation
  • Whole exome sequencing

Genomic Unity® Testing

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

Genomic Unity® Testing

Variantyx Genomic Unity® testing identified a de novo, heterozygous, pathogenic 2.9Mb inversion of 2q31.3 to 2q33.1.

The inversion includes exons 5-11 of the SATB2 gene and is predicted to result in loss-of-function of the protein.

Diagnosis: Glass syndrome

IGV view of SATB2 inversion

Uniform data from WGS clearly shows the inversion breakpoint.

The Variantyx Difference

Why was this inversion detected by Genomic Unity® testing, and not detected by other tests?

  • Balanced rearrangements like inversions are undetectable by most available technologies – including CMA, MLPA, gene panel and exome tests.
    Variantyx genome analysis detects many types of structural variants including copy number variants, deletions/duplications, inversions, mobile element insertions, regions of homozygosity and aneuploidy.

  • While inversions can be detected by karyotype, the size (2.9Mb) is below the limit of detection.
    Variantyx genome analysis has a detection range from 1bp to whole chromosomal events.

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

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