ONE TEST, DUAL DIAGNOSIS
IriSight® Case Study

COL11A1 splicing variant and TBC1D8B two-exon deletion provide a comprehensive diagnostic picture

Clinical presentation

A multigravida underwent an anatomy scan at 22 weeks gestation. The findings were concerning for skeletal dysplasia, including:

  • Micromelia
  • Foreshortened long bones
  • Frontal bossing
  • Depressed nasal bridge

Previous genetic testing

No previous genetic testing was reported.

IriSight® Testing

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

Results and interpretation

Variantyx IriSight® testing identified a heterozygous, pathogenic splicing variant in the COL11A1 gene. Duo analysis shows the variant is not maternally inherited.

Testing also identified a hemizygous, maternally inherited, likely pathogenic 5.14 kb deletion encompassing TBC1D8B  exons 13-14.

Diagnosis: Marshall syndrome, Nephrotic syndrome type 20

IGV view of COL11A1 SNV and TBC1D8B deletion variants

Uniform data from WGS clearly shows both the COL11A1 splicing variant (left) and the 5.14 kb deletion in the TBC1D8B gene (right).

The Variantyx Difference

Why is “standard” testing not enough? Why is IriSight® the ONLY test that can provide a complete diagnosis?

  • The size of both the single nucleotide variant and the 5.14 kb deletion fall below the cut-off value for CMA (~25 kb) and would not have been detected.

  • While exome sequencing may have detected the splicing variant and provided the Marshall syndrome diagnosis, deletions <3 exons in size are often missed – especially when both breakpoints are located within an intron. 

  • Without detection of the maternally inherited TBC1D8B deletion, the impact of Nephrotic syndrome type 20 on this – and possible future pregnancies – would have gone undetected.

    Variantyx genome analysis detects all major variant types in a single test including small sequence changes, mitochondrial variants, repeat expansions and structural variants.

    Only Variantyx genome analysis was able to provide both diagnoses, detecting both variants with a single test.

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