Personalized genome sequencing doubles the rate of diagnosis of rare diseases

Researchers at University College London (UCL) recently published an article in the journal Nature Communications that tailoring whole genome sequencing analysis to individual patients can double the diagnostic rate of rare diseases
.

In 2018, the UK Department for Health announced an NHS genomic medicine service that allows rare disease patients to read their entire genetic code in order to provide a much-needed diagnosis
.
However, interpreting these data can be challenging
.
Many people with complex and rare genetic diseases still do not have molecular answers
.

Researchers at University College London hope to provide a better diagnosis
for such patients.
To do this, they tested how the NHS diagnostic laboratory's capacity could be improved by a genomic medicine team of specialists, bioinformaticians and scientists, rather than just relying on standard, semi-automated data analysis
.

The research team re-evaluated undiagnosed cases to identify clues
that could hopefully guide personalized analysis.
Subsequently, they employed more bioinformatics methods, using advanced computer techniques to identify genetic alterations in patients' DNA that could lead to disease but were overlooked in routine testing
.

The study included 102 undiagnosed patients suspected of having primary mitochondrial disease, a group of incurable genetic disorders linked to a range of health problems, severe disability and shortened
lifespan.
The patients have been sequenced
whole genome through the NHS's 100,000 Genomes Project.

After the adoption of personalized analysis methods, the diagnostic rate increased from 16.
7% to 31.
4%.

The researchers also detected potentially disease-causing variants
in another 3.
9 percent of patients.

Co-corresponding author Dr Robert Pitceathly, from the Queens Square Institute of Neurology, University College London, said: "The NHS has invested heavily in advanced genetic technology
.
As a result, the UK has established itself at
the forefront of whole genome sequencing diagnostics.
However, some patients with rare genetic diseases still do not receive a molecular diagnosis
after genomic analysis.
”

"We believe it is critical to invest in a dedicated genomic medicine team to help gain multidisciplinary expertise and maximize diagnostic yields
.
On average, patients in our study wait more than 30 years to be diagnosed – we now have the capacity to tackle such cases, but adequate manpower planning is needed to support NHS diagnostic laboratories to achieve this
.
”

For patients, the diagnosis is important because they are able to use this result to plan their family, choose artificial insemination and participate in clinical trials
.
Dr Pitceathly said: "In this study, each new genetic diagnosis has a direct impact on patient care, including additional tests for heart problems, hearing loss and diabetes, as well as participation in clinical trials
.
”

Rachel North, one of the patients involved in the trial, believes the diagnosis was "life-changing.
"
Since then, she has been screened for complications of the disease, such as osteoporosis, which are treated
.

"I've been to a lot of hospitals over the last 20 years and spent a long time looking for the cause
.
I never thought I'd get a diagnosis one day," Rachel said
.

She added: "I'm worried about my 12-year-old son and if my condition will affect him
.
So knowing that this is a rare recessive genetic disease is a relief for me and removes the fear
of the unknown.
With the diagnosis, I can study my condition and manage
it very actively.
”

Dr James Davison, from the Department of Metabolic Medicine at Great Ormond Street Children's Hospital, said: "The process of diagnosing children and adults with rare, complex diseases can be a very lengthy process, and genomic medicine provides a transformative and powerful tool
to achieve this.
”

"This study highlights the importance of collaboration between clinicians and genetic scientists in interpreting genome sequencing results, promising to maximize the chances of diagnosis and thus help guide healthcare management and treatment choices
.
"

Original search

Macken, W.
L.
, Falabella, M.
, McKittrick, C.
et al.
Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing.
Nat Commun 13, 6324 (2022).
https://doi.
org/10.
1038/s41467-022-32908-7