Found by Others, Missed by Us

16-year-old male

DMD inversion provides genetic diagnosis, enabling access to treatment options.

Clinical Presentation

A 16-year-old male presented with a clinical diagnosis of Duchenne muscular dystrophy based on muscle biopsy results and hallmark symptoms, including:

  • Motor developmental delays, large calves, toe walking, frequent falls, loss of independent ambulation at age 10
  • Elevated CK levels
  • Restrictive lung disease

He has been excluded from DMD trials and vamorolone treatment was not covered due to lack of a molecular diagnosis.

Previous Genetic Testing

Multiple tests were performed including:

  • DMD gene sequencing – x2
  • DMD del/dup analysis – x2
  • Dystroglycan-related congenital muscular dystrophy panel

All tests were negative.

Results and Interpretation

Variantyx genome analysis identified a hemizygous pathogenic 713kb inversion encompassing exons 45-57 of the DMD gene.

It is expected to result in loss of function which is consistent with prior RNA analysis identifying an intronal inclusion that leads to an inability to produce dystrophin.

Diagnosis:

Duchenne muscular dystrophy

Uniform data from WGS identifies the breakpoints of the 713kb inversion spanning DMD exons 45-57.

The Variantyx Difference

Why was this inversion detected by Variantyx genome analysis, and not detected by other targeted DMD tests?

1

Balanced rearrangements like inversions are undetectable by most available technologies – including MLPA and targeted gene sequencing.

Variantyx genome analysis detects many types of structural variants including copy number variants, deletions/duplications, inversions, mobile element insertions, regions of homozygosity and aneuploidy.

2

Both inversion breakpoints are intronic, adding to the complexity of detection.

Variantyx genome analysis includes intronic regions, enabling breakpoint detection regardless of location.

Relevant Variantyx Tests

Variantyx tests that would have identified this variant include: