Rare disease day

January 2, 2021 | Genomic

An end to the rare disease diagnosis labyrinth

For many individuals, receiving a diagnosis for even common medical conditions can be tricky.

Doctors’ appointments need to be made, tests need to be run. But for those with rare diseases, where sometimes only a handful of other people in the entire world have the same condition, finding an accurate diagnosis can take years – even decades. Unfortunately, these individuals often find themselves forced into a medical labyrinth with no clear diagnosis in sight.

Rare diseases are classified as those that affect only a very small portion of the population. In Europe, for example, diseases are considered rare if they affect only 1 in every 2000 people. However, rare as each of these diseases might be, the true toll of these conditions goes far beyond these seemingly small numbers. In fact, because there are estimated to be between 6000 – 7000 different rare diseases, over 400 million people globally are affected by rare diseases.

Around 80% of these diseases are genetic and typically first appear during childhood. Because these conditions are so uncommon and feature a huge constellation of different symptoms, they are extremely challenging to diagnose using standard phenotypic methods. As a result, patient surveys suggest that individuals with rare diseases are often misdiagnosed and may wait anywhere from 5 to 30 years to receive a correct diagnosis. What’s more, many patients may never receive an accurate diagnosis. Without a diagnosis and an appropriate treatment plan, individuals with rare diseases face increased morbidity and mortality.

However, recent advances in whole exome sequencing (WES) technology and its clinical application are helping patients navigate the diagnosis labyrinth. Indeed, next generation sequencing approaches like WES are quickly becoming a first-line option for diagnosing unknown conditions. Further, as 85% of disease-causing mutations are located in coding regions of the genome, WES is a particularly promising tool for diagnosing rare diseases. One of the earliest successful applications of WES for rare disease diagnosis in the clinic occurred in 2011. When all other diagnostic avenues had been exhausted for a child with an intractable inflammatory bowel condition, clinicians turned to WES analysis. WES revealed that the child carried a novel mutation in X-linked inhibitor of apoptosis, allowing the clinicians to develop a treatment plan that saved the boy’s life.

Since then, next generation sequencing methods, including WES, have proven successful in increasing the number of rare diseases diagnoses, as well as drastically reducing the time-to-diagnosis. In fact, it’s been estimated that WES has the potential to identify greater than 95% of disease-causing, single-locus variants. As researchers, including those at QIAGEN, continue to develop increasingly efficient and accurate WES and bioinformatics tools, a greater number of patients will see the benefits of this technology.

Researchers and decision makers worldwide can further contribute to improving the lives of individuals with rare diseases and their families by participating in Rare Disease Day. This awareness-raising tribute was first organized in 2008 by EURORDIS (Rare Diseases Europe) and the Council of National Alliances to help inform the public about rare diseases and individuals’ struggles to find diagnoses and treatments. The first Rare Disease Day occurred in Europe on February 29, an unusual date that only occurs once every four years. Now Rare Disease Day is celebrated on the last day of February in over 100 countries.

This year, QIAGEN will be hosting a virtual event to commemorate Rare Disease Day, focused on the use of exome sequencing in rare disease research. Join us for exciting presentations from invited guests and our resident experts to hear the latest innovations, insights and best practices in exome sequencing. Look out for more information on this virtual event soon!

Want to learn more about how you can get involved with Rare Disease Day? Click through to find out how!

  1. Bick, D. et al. (2019) Case for genome sequencing in infants and children with rare, undiagnosed or genetic diseases. J. Med. Genet. 56, 783-791. doi:10.1136/jmedgenet-2019-106111
  2. Prokop, J. W. et al. (2018) Genome sequencing in the clinic: the past, present, and future of genomic medicine. Physiol. Genomics. 50, 563-579. doi:10.1152/physiolgenomics.00046.2018
  3. Sawyer, S L et al. (2016) Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin. Genet. 89, 275-84. doi:10.1111/cge.12654
  4. Shamseldin, H et al. (2017) Increasing the sensitivity of clinical exome sequencing through improved filtration strategy. Genet. Med. 19, 593–598. https://doi.org/10.1038/gim.2016.155
  5. Wise, Anastasia L et al. (2019) Genomic medicine for undiagnosed diseases. Lancet. 394, 533-540. doi:10.1016/S0140-6736(19)31274-7
  6. Rare Disease Day www.rarediseaseday.org/article/what-is-rare-disease-day
  7. RARE Facts globalgenes.org/rare-facts