A collaboration between Karolinska Institutet, Karolinska University Hospital, and SciLifeLab has integrated whole genome sequencing into routine diagnostic investigations for rare diseases at Karolinska University Hospital.
To date, more than 15,000 patients have had their entire genome sequenced, with 23% receiving a genetic diagnosis, according to a study published in Genome Medicine.
The study describes how, over the past decade, Karolinska University Hospital and SciLifeLab have developed a model in which whole genome sequencing is integrated into the diagnostic evaluation of patients with suspected rare diseases. It summarises data from 15,644 individuals and demonstrates how close collaboration between multidisciplinary clinical practice and advanced genomic analysis has enabled the implementation of whole genome sequencing into routine care.
Whole genome sequencing involves analysing the entire genome, providing a more comprehensive picture than tests that analyse only parts of the genome. The study shows that a genetic cause of disease could be identified in 3,538 individuals, corresponding to 23%. These diagnoses involved variants in more than 1,500 different genes, highlighting the diversity and complexity of rare diseases.
“For many patients with suspected rare diseases, receiving a genetic diagnosis is highly significant. It can provide an explanation for their condition and help guide treatment, follow‑up, and family planning. Whole genome sequencing allows us to detect genetic changes that would otherwise remain unnoticed,” said Anna Lindstrand, adjunct professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior consultant and head of section at Clinical Genetics and Genomics, Karolinska University Hospital.
The patients who received a diagnosis had a wide range of conditions across different medical specialties. A large proportion were children, and the majority would not have received a diagnosis without the new multidisciplinary approach, according to the researchers.
“In several cases, for example, in congenital metabolic disorders and severe epilepsies, we have been able to offer targeted treatment as a direct result of the diagnosis, preventing severe disease or early death,” said Anna Wedell, professor at the same department, senior consultant at Karolinska University Hospital, and director of Precision Medicine Center Karolinska.
The model is based on cooperation between clinical specialists, geneticists, bioinformaticians, and laboratory staff. This allows analyses to be tailored to each patient’s unique clinical presentation, with results rapidly translated into individualised care.
“By bringing together clinical medicine and advanced genomics, we have established a joint approach. I see this as part of a broader shift in the healthcare system towards more precise and personalised care in Sweden, and the model could form an important foundation for that development,” Wedell said.