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

Partial exon deletion plus deep intronic SNV explains juvenile parkinsonism

Clinical presentation

A 16-year-old male presented with a history of dopa-responsive juvenile parkinsonism/dystonia since the age of four. Additional symptoms included:

  • Oculogyric crises
  • Diurnal fluctuation of symptoms
  • Learning delays
  • Possible neurotransmitter metabolic disorder

Previous genetic testing

Multiple tests were performed with negative results including:

  • TH gene sequencing
  • Dystonia panel
  • 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 compound heterozygous variants in the TH gene: a likely pathogenic, paternally inherited 554bp deletion impacting part of exon 2 and a likely pathogenic, maternally inherited intronic SNV >300bp from an exon/intron boundary.

Diagnosis: Segawa syndrome

IGV view of TH variants

Uniform data from WGS clearly shows the intronic SNV (left) and 554bp deletion (right).

The Variantyx Difference

Why were both of these variants detected by Genomic Unity® testing, and not detected by other tests?

  • Gene sequencing is unlikely to detect CNVs like this deletion and would need to have been paired with MLPA for better likelihood of detection.
    Panels are typically unable to detect deletions smaller than 1 exon in size.
    Exomes are typically unable to detect deletions smaller than 3 exons in size.
    Variantyx genome analysis has a detection range from 1bp to whole chromosomal events, easily detecting this 554bp deletion.

  • One deletion breakpoint is intronic, adding to the complexity of detection.
    Variantyx genome analysis includes intronic regions, enabling breakpoint detection regardless of location.

  • The SNV falls outside of the 10-20bp of intronic sequence flanking exon/intron boundaries that is sometimes targeted by panel and exome assays.
    Variantyx genome analysis includes the full intronic sequence, enabling detection of characterized variants anywhere within the intron.

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