Genomic Unity® 2.0 Case Study
Overview
Patient:
2-year-old male
Clinical presentation:
Global developmental delays, exophoria, highly elevated alkaline phosphatase, severe congenital hypotonia, strabismus, multiple phenotypic anomalies including relative macrocephaly, high forehead, pectus excavatum and more
Testing strategy:
Variantyx whole genome testing
Key finding:
De novo, heterozygous, pathogenic 10.54 kb deletion in the GRIA2 gene
Clinical outcome:
Diagnosis established
Why Genomic Unity® 2.0 was the right choice
Despite a prior negative exome, the patient’s severe hypotonia, exophoria, developmental delays and distinctive features were strongly suggestive of an underlying genetic condition. When a highly elevated alkaline phosphatase level was identified, suspicion grew for a hyperphosphatasia with impaired intellectual development syndrome, despite the absence of classical physical findings.
Genomic Unity® 2.0 was selected because it delivers the most comprehensive genomic insight from the start while:
- Reducing time to diagnosis
- Avoiding unnecessary testing
- Supporting the highest standard of patient care
Diagnostic finding: GRIA2-related neurodevelopmental disorder
Variantyx Genomic Unity® 2.0 testing identified a de novo, heterozygous, pathogenic 10.54 kb deletion in the GRIA2 gene.
Encompassing the 5′ UTR and a portion of exon 1, the deletion is expected to result in loss of protein function.
Uniform data from both short-read WGS (top) and long-read WGS (bottom) clearly show the deletion, with long-read WGS providing precise sizing of 10,539 bp.
Testing also identified a mitochondrial MT-RNR1 variant (not shown).
Impact on clinical care
Established an elusive diagnosis, distinct from the suspected hyperphosphatasia disorder. Additionally identified antibiotics to avoid that could lead to hearing loss.
Variant spotlight: Partial exon deletions
Detection challenges:
Partial exon deletions are below the limit of detection of most genetic tests – including exome and panel tests. Especially when one or both breakpoints fall within an intronic or intergenic region. This leads to missed variant calls.
Why Genomic Unity® 2.0
- Has a detection range from 1 bp to whole chromosomal events, easily detecting partial exon deletions.
- Sequences all intronic and intergenic regions, enabling breakpoint detection regardless of location.
Additional similar cases
Genomic Unity® – Partial exon deletion explains clinical Rett syndrome diagnosis
Genomic Unity® – Partial exon deletion plus deep intronic SNV explains juvenile parkinsonism
IriSight® – Partial DOK7 deletion plus small indel explains multiple fetal anomalies
Variantyx tests that would have identified this variant
Genomic Unity® 2.0 | Genomic Unity® Whole Genome Analysis | Genomic Unity® Lightning Genome Analysis | Genomic Unity® Lightning 2.0 Genome Analysis – NICU | Genomic Unity® Lightning 2.0 Genome Analysis – Standard | Genomic Unity® Exome Plus Analysis | Genomic Unity® Exome Analysis | Genomic Unity® Constitutional Genome-Wide Copy Number Variant Analysis | Genomic Unity® Genome-Wide CNV and FMR1 Analysis