Case Study: Adult-onset phenotype with a dual diagnosis

PerkinElmer Genomics offers whole genome sequencing (WGS) for every need: standard, prenatal, STAT, and ultrarapid. The clinical utility and relevance of WGS cannot be overstated. As demonstrated by this real case study from our laboratory, comprehensive WGS can finally bring answers to patients, families, and providers.

Testing History

• Repeat expansion evaluation for spinocerebellar ataxias (SCA) 1,2,3,6,7,8,10,17, dentatorubral-pallidoluysian atrophy (DRPLA) and Fragile X – NEGATIVE
• Gene sequencing for spinocerebellar ataxia (SCA) 5, 12, 13, 14, 28 –NEGATIVE
• Clinical whole exome sequencing (WES) – NEGATIVE

Following negative extensive workup results, whole genome sequencing was ordered

PerkinElmer Genomics Whole Genome Sequencing Results

Interpretation

Whole genome sequencing identified two pathogenic variants: SPG7 variant associated with neurologic abnormalities and a TRNS1 (MT-TS1) variant in the mitochondrial DNA (mtDNA) associated with mitochondrial encephalopathy with cytochrome c oxidase deficiency.

This dual diagnosis explains the patient’s blended phenotype. SPG7 pathogenic variants have been reported in autosomal dominant and recessive spastic paraplegia.¹ This variant has been reported without a second pathogenic variant in a patient with progressive gait difficulties, muscle weakness, and spasticity. The pathogenic TRNS1 (MT-TS1) variant has been reported to result in ataxia, dysarthria, myoclonic epilepsy, and sensorineural hearing loss.²

Both diagnoses are crucial for accurate risk assessment & pre-symptomatic testing for family members

Incorporation of mitochondrial DNA analysis is one of the advanced features of PerkinElmer Genomics’ whole genome sequencing tests. As this case demonstrates, mtDNA analysis can play a key role in reaching a diagnosis for patients with progressive, complex neurologic phenotypes. This comprehensive approach to whole genome sequencing is just one reflection of PerkinElmer Genomics’ commitment to answering the most challenging genetic questions to proactively inform patient care, improve patient quality of life, and end the diagnostic odyssey for families.

Impact Patient Care with PerkinElmer Genomics Whole Genome Sequencing

PerkinElmer Genomics provides whole genome testing options spanning the full continuum of care — from prenatal to neonatal & pediatrics to adult. With a depth of resources like patient-friendly test guides, online ordering portal, flexible specimen collection kits, and billing and payment options that offer financial peace of mind, PerkinElmer Genomics is here to assist you with the seamless implementation of whole genome sequencing in your practice.

REFERENCES

1. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 602873: 03/15/2021: https://www.omim.org/entry/602783
2. Online Mendelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM Number: 590080: 09/17/2013: https://www.omim.org/entry/590080
3. Lionel AC, Costain G, Monfared N, et al. Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test. Genet Med. 2018;20(4):435-443. doi:10.1038/gim.2017.119