Single test for over 50 genetic diseases will cut diagnosis from decades
to days
Validating genetic diagnosis of neurological and neuromuscular diseases
using faster, smaller, cheaper sequencing technologies

Date:
March 4, 2022
Source:
Garvan Institute of Medical Research
Summary:
A single DNA test has been developed that can screen a patient's
genome for over 50 genetic neurological and neuromuscular
diseases such as Huntington's disease, muscular dystrophies and
fragile X syndrome. The new test avoids a 'diagnostic odyssey'
for patients that can take decades. The team has shown that the
test is accurate. They are now working on validations to make
it available in pathology labs. They expect it to be standard in
global pathology labs within five years.



FULL STORY ==========================================================================
A new DNA test, developed by researchers at the Garvan Institute
of Medical Research in Sydney and collaborators from Australia, UK
and Israel, has been shown to identify a range of hard-to-diagnose
neurological and neuromuscular genetic diseases quicker and
more-accurately than existing tests.


==========================================================================
'We correctly diagnosed all patients with conditions that were already
known, including Huntington's disease, fragile X syndrome, hereditary cerebellar ataxias, myotonic dystrophies, myoclonic epilepsies,
motor neuron disease and more,' says Dr Ira Deveson, Head of Genomics Technologies at the Garvan Institute and senior author of the study.

The diseases covered by the test belong to a class of over 50 diseases
caused by unusually-long repetitive DNA sequences in a person's genes --
known as 'Short Tandem Repeat (STR) expansion disorders'.

'They are often difficult to diagnose due to the complex symptoms
that patients present with, the challenging nature of these repetitive sequences, and limitations of existing genetic testing methods,' says
Dr Deveson.

The study, published today in Science Advances, shows that the test
is accurate, and allows the team to begin validations to make the test available in pathology services around the world.

A patient who participated in the study, John, first realised something
wrong when he experienced unusual problems balancing during a ski lesson.



==========================================================================
'It was very worrying having symptoms that, over the years, increased in severity; from being active and mobile to not being able to walk without support. I had test after test for over ten years and absolutely no
answers as to what was wrong,' says John, who was eventually diagnosed
with a rare genetic disease called CANVAS, which affects the brain.

'It was reassuring to finally confirm my diagnosis genetically, and it's exciting to know that, in the near future, others with these types of conditions will be able to get a diagnosis quicker than I did,' he says.

'For patients like John, the new test will be a game-changer, helping
to end what can often be a taxing diagnostic odyssey,' says Dr Kishore
Kumar, a co- author of the study and clinical neurologist at the Concord Hospital.

Repeat expansion disorders can be passed on through families, can be
life threatening and generally involve muscle and nerve damage, as well
as other complications throughout the body.

Quicker, more-accurate diagnosis for patients avoids 'diagnostic odyssey' Current genetic testing for expansion disorders can be 'hit and miss',
says Dr Kumar. 'When patients present with symptoms, it can be difficult
to tell which of these 50-plus genetic expansions they might have, so
their doctor must decide which genes to test for based on the person's
symptoms and family history. If that test comes back negative, the
patient is left without answers.

This testing can go on for years without finding the genes implicated
in their disease. We call this the 'diagnostic odyssey', and it can be
quite stressful for patients and their families,' he says.



========================================================================== 'This new test will completely revolutionise how we diagnose these
diseases, since we can now test for all the disorders at once with a
single DNA test and give a clear genetic diagnosis, helping patients
avoid years of unnecessary muscle or nerve biopsies for diseases they
don't have, or risky treatments that suppress their immune system,'
says Dr Kumar.

Although repeat expansion disorders cannot be cured, a quicker diagnosis
can help doctors identify and treat disease complications earlier,
such as heart issues associated with Friedreich's ataxia.

Scanning for known and novel diseases Using a single DNA sample, usually extracted from blood, the test works by scanning a patient's genome
using a technology called Nanopore sequencing.

'We've programmed the Nanopore device to hone in on the roughly 40 genes
known to be involved in these disorders and to read through the long,
repeated DNA sequences that cause disease,' he says. 'By unravelling the
two strands of DNA and reading the repeated letter sequences (combinations
of A, T, G or C), we can scan for abnormally long repeats within the
patient's genes, which are the hallmarks of disease.' 'In the one test,
we can search for every known disease-causing repeat expansion sequence,
and potentially discover novel sequences likely to be involved in diseases
that have not yet been described,' says Dr Deveson.

Upscaling to wider use in the next five years The Nanopore technology
used in the test is smaller and cheaper than standard tests, which the
team hopes will smooth its uptake into pathology labs. 'With Nanopore,
the gene sequencing device has been reduced from the size of a fridge to
the size of a stapler, and costs around $1000, compared with hundreds
of thousands needed for mainstream DNA sequencing technologies' says
Dr Deveson.

The team expects to see their new technology used in diagnostic practice
within the next two to five years. One of the key steps towards that
goal is to gain appropriate clinical accreditation for the method.

Once accredited, the test will also transform research into genetic
diseases, says Dr Gina Ravenscroft, a co-author of the study and
a researcher working on rare disease genetics at the Harry Perkins
Institute of Medical Research.

'Adult-onset genetic disorders haven't received as much research
attention as those that appear in early life,' she says. 'By finding
more people with these rare adult-onset diseases, and those who may be pre-symptomatic, we'll be able to learn more about a whole range of rare diseases through cohort studies, which would otherwise be hard to do.'
The work was supported predominantly byphilanthropic funding from The
Kinghorn Foundation.

========================================================================== Story Source: Materials provided by
Garvan_Institute_of_Medical_Research. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Igor Stevanovski, Sanjog R. Chintalaphani, Hasindu Gamaarachchi,
James M.

Ferguson, Sandy S. Pineda, Carolin K. Scriba, Michel Tchan, Victor
Fung, Karl Ng, Andrea Cortese, Henry Houlden, Carol Dobson-Stone,
Lauren Fitzpatrick, Glenda Halliday, Gianina Ravenscroft, Mark
R. Davis, Nigel G. Laing, Avi Fellner, Marina Kennerson, Kishore
R. Kumar, Ira W.

Deveson. Comprehensive genetic diagnosis of tandem repeat expansion
disorders with programmable targeted nanopore sequencing. Science
Advances, 2022; 8 (9) DOI: 10.1126/sciadv.abm5386 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220304144646.htm

--- up 4 days, 10 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)