MISSED BY OTHERS, DETECTED BY US
IriSight® Case Study

De novo indel explains hypoplastic left heart

Clinical presentation

Multiple anomalies were noted on a routine ultrasound including:

  • Hypoplastic left heart
  • Cystic hygroma
  • Hydrops fatalis
  • Echogenic kidneys and bowel

Previous genetic testing

A typical work-up for hypoplastic left heart syndrome is long, with multiple possible genetic causes including aneuploidies, CNV disorders and single gene disorders. Multiple tests were performed with negative results including:

  • Karyotype
  • SNP microarray
  • 30 gene cfDNA panel

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 de novo, heterozygous, pathogenic, single nucleotide deletion in the KMT2D gene.

The nucleotide deletion likely results in a frameshift which causes truncation of the protein.

Diagnosis: Kabuki syndrome

IGV view of KMT2D variant

Uniform data from WGS clearly shows the single nucleotide deletion.

The Variantyx Difference

Why was this single nucleotide deletion detected by IriSight® testing, and not detected by other tests?

  • Indels are below the limit of detection of karyotype (typically 4-5 Mb) and SNP microarray (typically 50-250 kb in clinically relevant regions) tests.
    Variantyx genome analysis has a detection range from 1 bp to whole chromosomal events, easily detecting this small sequence change.

  • The KMT2D gene is not included in the 30 gene cfDNA panel test that was performed, nor is it included in similar tests offered by other providers.
    Variantyx genome analysis does not exclude any gene.

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