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

Single exon deletion explains epilepsy and developmental delay

Clinical presentation

A 2-year-old male presented with a history of severe, early-onset seizures and global developmental delay:

4 weeks old – Tonic clonic seizures
2 months old – Global developmental delay
22 months old – Difficulty swallowing, unable to sit or roll over, right side seems stronger than his left, cortical visual impairment, hypotonia, abnormal electroencephalogram (EEG), relative microcephaly

Multiple tests were performed with negative results including:

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

Variantyx Genomic Unity® testing identified a de novo, hemizygous, pathogenic 2.1 kb deletion that spans exon 7 of the CDKL5 gene.

The deletion is mosaic, present in ~40% of reads for this X-linked gene.

Diagnosis: Developmental and epileptic encephalopathy 2 (DEE2)

Uniform data from WGS clearly shows the mosaic, 2.1 kb deletion.

Why was this single exon deletion detected by Genomic Unity® testing, and not detected by other tests?

CMA tests are unable to detect deletions smaller than 25kb.
Targeted tests like the epilepsy panel ordered are typically unable to detect deletions smaller than 500bp. While the full size of the deletion is 2,123bp, the exonic portion is only 121bp.
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 2.1 kb deletion.
Both deletion breakpoints are intronic, adding to the complexity of detection.
Variantyx genome analysis includes intronic regions, enabling breakpoint detection regardless of location.

Connect with a Clinical Specialist to find out how easy it is to bring the power of whole genome sequencing into your practice.