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

Partial exon deletion explains clinical Rett syndrome diagnosis

Clinical presentation

A 9-year-old female with a clinical diagnosis of Rett syndrome presented with a history of global developmental delay with regression and an array of symptoms:

  • Microcephaly
  • Quadriparesis and quadriplegia with a history of infantile hypotonia
  • Seizures and tremors
  • Nonverbal with a history of speech difficulty

Previous genetic testing

Multiple tests were performed with negative results including:

  • Chromosomal microarray (x2)
  • Epilepsy panel
  • Rett/Angelman syndrome panel, PWS/AS methylation
  • SCN1A and MTHFR gene sequencing
  • Whole exome sequencing, multiple reanalyses
  • Whole genome sequencing

Genomic Unity® Testing

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

Genomic Unity® Testing

Variantyx Genomic Unity® testing identified a heterozygous, pathogenic 453bp deletion affecting the final exon of the MECP2 gene.

The deletion is predicted to result in absent or dysfunctional protein.

Diagnosis: Rett syndrome

IGV view of MECP2 deletion

Uniform data from PCR-free WGS clearly shows the 453bp partial exon deletion.

The Variantyx Difference

Why was this partial 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 and Rett/Angelman syndrome panels ordered are typically unable to detect deletions smaller than 500bp.

  • Exomes are typically unable to detect deletions smaller than 3 exons in size, particularly in poorly covered regions such as this region of MECP2.

  • Other genome analyses are typically unable to detect deletions smaller than 1kb.
    Variantyx genome analysis has a detection range from 1bp to whole chromosomal events, easily detecting this 453bp deletion.

  • One of the deletion breakpoints is intronic, adding to the complexity of detection.
    Variantyx genome analysis includes intronic regions, enabling breakpoint detection regardless of location.

Want similar results for your patients?

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

Request a consultation