Personalized whole genome sequencing doubles the diagnosis of rare diseases

A new scientific study has found that personalized whole genome sequencing can double
the diagnostic rate of rare diseases.

A new study led by researchers at University College London (UCL) has found that tailoring whole genome sequencing analysis to individual patients can double
the diagnostic rate of rare diseases.

In 2018, the UK Department of Health announced a National Health Service (NHS) Genomic Medicine Service that allows patients with rare diseases to read their entire genetic code, hoping to provide much-needed diagnoses
.

However, interpreting these data can be unusually challenging
.
In fact, many people with complex, rare genetic diseases still don't get molecular answers
about the cause of their problems.

In this study, the researchers sought to give such patients a better chance of
receiving a genetic diagnosis.
The study, conducted at the London Mitochondrial Centre at the Queens Square Institute for Neurological Research at University College London and the Great Ormond Street Child Health Institute at University College London, will be published today (7 November) in the journal Nature Communications
.

To achieve their goal, the researchers tested how genomic medicine teams made up of specialist doctors, bioinformaticians, and scientists could be used to improve the capabilities of NHS diagnostic laboratories, not just standard semi-automated data analysis
.
The UCL team re-evaluated the unconfirmed cases to identify clues
that might help guide further, more personalised analysis.
They then applied additional bioinformatics methods, using advanced computer technology to identify genetic alterations in the patient's DNA that could cause disease but were overlooked in routine testing
.
Participants in the study included 102 undiagnosed patients suspected of having primary mitochondrial disease (a large array of incurable genetic diseases that affect children and adults and are linked to a wide range of medical problems, severe disability and shortened lifespan) who had whole genome sequencing
through the NHS's 100,000 Genomes Programme.
This personalized approach increased the diagnostic rate from 16.
7% to 31.
4%.

It also detected potentially pathogenic variants
in another 3.
9 percent of patients.

Lead author Dr Robert Pitceathly, co-head of the NHS London's Highly Specialised Service for Rare Mitochondrial Diseases and Head of the Research Group at the Queenssquare Institute of Neurological Research at 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 diagnostic whole genome sequencing.
That said, some people with rare genetic diseases still don't get a molecular diagnosis
after genomic analysis.
We believe it is critical to invest in a dedicated genomic medicine team to ensure equitable access to dedicated multidisciplinary expertise and maximize
diagnostics.
In our study, patients waited an average of more than 30 years for diagnosis – we now have the capacity to address such cases, but adequate manpower planning is needed to support NHS diagnostic genomics laboratories to achieve this
.
”

Receiving a genetic diagnosis is important because it gives patients access to family planning, specialized IVF, and drug testing
.
It can also enable targeted screening for known disease complications and conduct drug research
.

Dr Pitceathly said: "In this study, each new genetic diagnosis has a direct impact
on patient care.
This includes additional tests for heart problems, hearing loss and diabetes, as well as the opportunity to
participate in clinical trials.
”

Professor Michael Hanna, Director of the Institute of Neurological Research in Queenssquare at University College London, said: "This work is an important step
forward in developing the best way for patients to maximise the benefits of genomic analysis.
It clearly shows that by combining automated methods of genomic analysis with data interpretation by skilled multidisciplinary teams, diagnostic rates have doubled
.
This is an important discovery that will influence the development of
genomic medical diagnostic services worldwide.
”

Study co-author Dr James Davison (Department of Metabolic Medicine, Great Ormond Street Hospital and Chair of the UK Inherited Metabolic Diseases Group) said: "The process of diagnosing children and adults with rare, complex diseases can be a very lengthy process, and genomic medicine offers a revolutionary and powerful tool
to help achieve this.
This study highlights the importance of collaboration between clinical experts and genetic scientists in interpreting genome sequencing results to maximize the chances of diagnosis to help guide medical management and treatment choices
.
”

“Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing” 7 November 2022, Nature Communications.