Genomic Unity® 2.0 Case Study
Overview
Patient:
14-month-old female
Clinical presentation:
Global developmental delay, failure to thrive, hypotonia
Testing strategy:
Variantyx whole genome testing with combined short and long-read sequencing
Key finding:
Maternal uniparental isodisomy with aberrant methylation
Clinical outcome:
Diagnosis established
Why Genomic Unity® 2.0 was the right choice
With a history of intrauterine growth restriction, the patient’s developmental delays were suspected to be genetic in origin.
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: Prader-Willi syndrome
Variantyx Genomic Unity® 2.0 testing identified maternal uniparental isodisomy (UPiD) of chromosome 15.
The MAGEL2 and SNURF regions are normally paternally expressed, but show hypermethylation consistent with maternal UPiD.
Methylation analysis of long-read sequencing data clearly distinguishes hypermethylated (predominately red) reads from normally methylated (mixed red and blue) reads.
Impact on clinical care
Established a definitive diagnosis, informing risk of recurrence.
Variant spotlight: Aberrant methylation
Detection challenges:
Short-read technologies like exome and standard genome sequencing are unable to detect DNA methylation – a key criteria for definitive diagnosis of imprinting disorders.
Why Genomic Unity® 2.0
- Sequences a patient’s genome twice: once with short-read genome sequencing and once with long-read genome sequencing.
- Long-read sequencing simultaneously detects genetic variants and DNA methylation enabling definitive diagnosis of Angelman, Prader-Willi and Fragile X syndromes.
Additional similar cases
Genomic Unity® 2.0 – Methylation analysis confirms paternal origin of MAGEL2 indel