A New Era in Rare Disease Diagnosis: How Whole Genome Sequencing is Providing Answers for Patients and Their Families

A New Era in Rare Disease Diagnosis: How Whole Genome Sequencing is Providing Answers for Patients and Their Families

Navigating the Complex World of Rare Diseases: The Importance of Genetics and Early Diagnosis

Rare diseases are a diverse group of over 8,000 distinct conditions, with the majority having a genetic origin. While each disease is uncommon, collectively, they impact a significant portion of the population, with a prevalence of 6-8%. These diseases can present with a wide range of symptoms, from mild to severe, with the nervous system often affected, leading to intellectual disability, neuropsychiatric diseases, epilepsy, and motor dysfunction. The age of onset can vary greatly, from prenatal to late adulthood, with half of the affected cases referred by paediatricians. Early diagnosis of rare diseases is crucial for optimal treatment, care, and genetic counselling regarding prognosis and recurrence risks. For example, this is especially true for diseases like inborn errors of metabolism, where specific treatments such as diets, recombinant enzymes, and small molecule drugs are available. The initiation of treatment in the early stages of the disease can sometimes prevent serious handicaps or early death, making rapid diagnostics essential.

 

Uncovering the Rarity: The Importance of Whole Genome Sequencing in Diagnosing Rare Diseases

Unfortunately, diagnosing rare diseases can be challenging, and most patients do not receive a genetic diagnosis. Currently, fewer than half of rare diseases have a known genetic cause, and even when the cause is known, the chances of a diagnosis can be low due to limited testing and an incomplete understanding of clinical manifestations. It is not uncommon for patients to see multiple physicians over several years before receiving a diagnosis. Fortunately, recent advances in genetic testing technology, such as Whole Genome Sequencing (WGS), which sequences a person's entire genome, have significantly increased the likelihood of making a genetic diagnosis for patients with rare diseases. For example, a study from the 100,000 Genomes Project published in the New England Journal of Medicine showed that WGS led to diagnoses for 25% of participants with rare genetic conditions. This approach was able to identify conditions that may have been missed by traditional diagnostic methods. Another recent study performed in 2022 by UCL researchers has shown that personalizing the analysis of WGS for patients could significantly increase the diagnosis rates of rare diseases. These breakthroughs in genetic testing have the potential to put an end to the long diagnostic odysseys that many patients with rare diseases have to go through while enabling more personalized clinical care and predictive testing for inherited conditions.

 

 How WGS can help patients affected by rare diseases

WGS is a comprehensive and cost-effective genetic testing method for rare diseases, with a higher diagnostic yield and improved operational efficiency compared to other methods. WGS can detect multiple variant types in a single assay, resulting in faster and more accurate diagnoses.

For instance, in a randomized trial, WGS reduced the median time to diagnosis from 107 days to 13 days in neonatal and pediatric intensive care patients. WGS is particularly valuable for certain rare diseases, such as primary mitochondrial disease phenotypes, a group of inherited disorders caused by mutations in mitochondrial or nuclear DNA. In these patients, WGS has been shown to improve the diagnostic rate from 16.7% to 31.4%. Moreover, WGS has played a critical role in identifying four previously unknown genetic variations linked to hereditary pulmonary arterial hypertension (PAH). This breakthrough has greatly advanced our understanding of the genetic basis of PAH and provides new insights into the underlying mechanisms of the disease, which could lead to the development of more effective treatments.

Overall, WGS is a valuable tool for identifying and treating rare diseases. WGS has the potential to not only improve diagnosis and treatment but also to advance our understanding of the underlying mechanisms of rare diseases.

 

Introducing the Rare Disease Health Package by Dantes Lab: Revolutionizing Rare Disease Diagnosis with WGS Testing

The Rare Disease Health Package offered by Dantes Lab uses WGS testing to provide a comprehensive view of a patient's genome. This approach can save time and money, identify potential treatments and management strategies, and provide closure for patients and their families who are struggling with the diagnostic odyssey of rare and undiagnosed diseases. The package includes Pre- and Post-Telemedicine Consultations with Specialist Doctors, providing access to specialists who may not be available in a patient's area and ensuring that patients are prepared for testing and stay on track with their treatment plan. Dantes Lab removes financial barriers to care by identifying potential treatments and management strategies for rare diseases. The package also prioritizes privacy and security, with a commitment to not selling genomic and personal information and compliance with GDPR and HIPAA regulations. The 30X Coverage Clinical-Grade Whole Genome Sequencing used in the package ensures high accuracy and confidence in the results, critical for identifying variants that may be causative of rare diseases or other conditions. Overall, the Rare Disease Health Package by Dantes Lab is a valuable tool in the fight against rare diseases, offering patients and their families the definitive diagnosis they need and allowing them to move forward with a better understanding of their condition. More information can be found at dantelabs.com. 

Take-home messages

  • Understand that rare diseases are a diverse group of over 8,000 distinct conditions, with the majority having a genetic origin;
  • Recognize that early diagnosis of rare diseases is crucial for optimal treatment, care, and genetic counselling regarding prognosis and recurrence risks;
  • Appreciate that recent advances in genetic testing technology, such as Whole-Genome Sequencing (WGS), have significantly increased the likelihood of making a genetic diagnosis for patients with rare diseases;
  • Discover how Dante Genomics' Rare Disease Health Package uses WGS to provide an invaluable tool in the fight against rare diseases, offering free Pre- and Post-Telemedicine Consultations with Specialist Doctors;
  • Visit dantelabs.com to learn more about how the Rare Disease Health Package and Whole Genome Sequencing (WGS) can help diagnose rare diseases.

 

 By Paduano Francesco, PhD

 

 

Resources

Turro, E.,  et al., (2020). Whole-genome sequencing of patients with rare diseases in a national health system. Nature, 583(7814), 96-102.

 https://doi.org/10.1038/s41586-020-2434-2

Macken, W. L. et al., (2022). Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing. Nature Communications13(1), 6324. https://doi.org/10.1038/s41467-022-32908-7

 100,000 Genomes Project Pilot Investigators. (2021). 100,000 genomes pilot on rare-disease diagnosis in health care—preliminary report. New England Journal of Medicine, 385(20), 1868-1880. https://www.nejm.org/doi/full/10.1056/NEJMoa2035790

Petrikin, J. et al., (2018). The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants. NPJ genomic medicine3(1), 6.

https://doi.org/10.1038/s41525-018-0045-8

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