Genomic Unity^® 2.0 Case Study

Variantyx. See more from the very first test.

Overview
Why Genomic Unity® 2.0
Diagnostic Finding
Variant Spotlight
Additional Similar Cases

Overview

Patient:  

8-year-old female

Clinical presentation: 

Polyphagia, obesity, atypical behavior around food, attention deficit hyperactivity disorder, deeply set eyes, hypertension

Testing strategy:

Variantyx whole genome testing with combined short and long-read sequencing

Key finding:

Heterozygous, likely pathogenic indel in the MAGEL2 gene on the paternal allele

Clinical outcome:

Diagnosis established

Why Genomic Unity® 2.0 was the right choice

While a genetic etiology was suspected, the patient’s non-specific clinical presentation made it difficult to identify a single, likely syndrome that would guide testing.

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: Schaaf-Yang syndrome

Variantyx Genomic Unity^® 2.0 testing identified a heterozygous, likely pathogenic c.528delG variant in the MAGEL2 gene. Using continuous long reads, the variant was determined to be in trans with maternally inherited rs850807 – therefore c.528delG resides on the paternal (Schaff-Yang syndrome associated) allele.

Methylation data is consistent with assignment of the variant to the paternal allele.

Methylated view of MAGEL2 reads

Methylation analysis of long-read sequencing data spanning the MAGEL2 region shows that the variant resides on predominantly non-methylated (blue) reads presumed to be paternal in origin.

Impact on clinical care

Established a definitive diagnosis.

Variant spotlight: 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 allele-specific resolution within the MAGEL2 imprinting region.