Update on Validations for PHOX2B and DMPK

Updates from Rady Children's Institute for Genomic Medicine on rapid Whole Genome Sequencing and more.

Rady Children’s Institute for Genomic Medicine is excited to announce that the current version of our rWGS®/urWGS test is now validated to include identification of repeat expansions in the PHOX2B gene, associated with Congenital Central Hypoventilation Syndrome (CCHS), and in the DMPK gene, associated with Myotonic Dystrophy Type 1 (DM1).

The sensitivity for detecting repeat expansions in the abnormal range within the carboxy terminal polyalanine repeat region of PHOX2B and within the 3’UTR of DMPK by WGS is > 90%.  However, because the exact number of repeats cannot currently be determined by short-read NGS sequencing, orthogonal confirmation for more accurate sizing is required prior to final reporting.  Confirmatory testing will be performed at an external CAP/CLIA laboratory, which may extend the timeline for final test result reporting.

Please note that:

  1. Due to the limitations of short-read NGS in accurately characterizing the repeat size in the DMPK gene, targeted testing should be considered if there is a strong clinical suspicion of myotonic dystrophy, even in the context of a negative RCIGM rWGS test result.
  2. Normal, nonexpanded alleles and alleles in the premutation range will not be reported in proband or parents.
  3. Inheritance for DMPK will only be reported for Trio test parents who screen positive for a DMPK repeat expansion in the abnormal range. Parental inheritance will not be reported for Solo genome sequencing test types.
  4. Preliminary reports may not be released for all positive DMPK findings, as some findings may screen positive but require orthogonal confirmation prior to reporting. However, a verbal communication on a suspected DMPK expansion will be provided to the clinical team by an RCIGM laboratory genetic counselor.
  5. Familial variant testing is not offered for DMPK or PHOX2B
  6. Comprehensive rWGS reanalysis requests will include DMPK and PHOX2B analysis, but the testing methodology does not support targeted reanalysis for these two genes.

Please contact us if you have any questions.

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