RARE Daily

Whole Genome Sequencing Enables Rare Disease Diagnoses

March 22, 2021

Rare Daily Staff

More than 1,200 people with rare diseases have received a diagnosis thanks to the integration of large-scale genomics into the Stockholm region’s healthcare system, a new study reports.

The study from Karolinska Institutet in Sweden analyzed the result of the first five years of collaboration on whole genome sequencing between Karolinska University Hospital and SciLifeLab. The report, published in Genome Medicine, adds to the case for whole genome sequencing’s ability to advance an era of precision medicine.

“We’ve established a way of working where hospital and university collaborate on sequencing each patient’s entire genome in order to find genetic explanations for different diseases,” said the paper’s first author Henrik Stranneheim, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet. “This is an example of how precision medicine can be used to make diagnoses and tailor treatments to individual patients.”

Large-scale whole genome sequencing technology has made rapid advances over the recent decade. Despite this, few clinics worldwide routinely use it to diagnose patients.

A little more than five years ago, the Karolinska University Laboratory and the Clinical Genomics facility at SciLifeLab launched the Genomic Medicine Center Karolinska-Rare Diseases, which involves researchers from among Karolinska Institutet and KTH Royal Institute of Technology.

In the first five years, the center carried out genome sequencing of 3,219 patients, which led to molecular diagnoses for 1,287 patients (40 percent) with rare diseases. The results are described in the Genome Medicine paper.

The researchers found pathogenic mutations in more than 750 genes and discovered 17 novel disease genes. In some cases, the findings have enabled personalized treatment for patients with, for example, inherited metabolic diseases, rare epilepsies, and primary immune deficiencies.

“Clinical whole genome sequencing has had huge implications for the area of rare diseases,” says Anna Wedell, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and one of the paper’s corresponding authors. “Used in the right way, targeted at each patient’s specific clinical situation, new groups of patients can receive the right diagnosis and treatment in a way that hasn’t been possible before.”

One challenge of whole genome sequencing is the need to manage and interpret the millions of genetic variants that exist in each individual. The center has developed a model that directs the initial analysis to pathogenic variants in genes deemed relevant for each patient’s clinical symptoms. This requires doctors to play an important role in deciding which genetic analyses should be done first.

If the first assessment fails to produce a result, the analysis is broadened to more gene panels until a diagnosis can be established and/or the whole genome is sequenced.

An effort is now underway to broaden the approach in the Swedish healthcare sector.

Photo: Henrik Stranneheim, researcher at the Department of Molecular Medicine and Surgery, Karolinska Institutet


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