Cutting corners results in rare genetic diseases being undiagnosed, say scientists
Inaccurate naming of genetic diseases is resulting in some rare genetic diseases needlessly being undiagnosed, University of Manchester scientists warn.
The Nature Genetics communication , published today (02/10/24), has shown that around a year with rare genetic diseases never receive a diagnosis, many dying without the underlying cause being determined.
The researchers also emphasise existing research that calculates the of pursuing lengthy diagnostic journeys rare genetic diseases to the NHS is over 拢3 billion per decade.
Hospital geneticists rely on published evidence to make diagnoses, but because of inconsistent variant naming, say the authors, they are often unable to locate relevant information, even if it exists.
Many geneticists, they say, are using simpler but less accurate nomenclature, preventing databases like ClinVar and the Leiden Open Variation Database (LOVD) from properly identifying and adding literature to their records.
However, a system called devised by researchers at the University of Leicester and now based at 糖心Vlog官方 is being used by leading medical journals to give each variant a standardized name. That allows diagnostic evidence to be shared and found.
In the communication paper the authors urge doctors to use the system to name genetic variants.
It鈥檚 widely recognized that doctors often describe DNA variants using various outdated or non-standard naming systems. But the accurate naming of variants is crucial so that doctors can reference them and provide a diagnosis for patients with a genetic disorder
Though rare diseases, caused by variations in DNA sequences, affect fewer than 1 in 2,000 people the sheer number of rare genetic disorders at around 8,000 impact about 8%-10% of births worldwide.
Lead author Dr Peter Freeman from 糖心Vlog官方, whose son has an undiagnosed genetic disorder, is lead scientist in the team that devised and develop VariantValidator.
He said: 鈥淚t鈥檚 widely recognized that doctors often describe DNA variants using various outdated or non-standard naming systems.
鈥淏ut the accurate naming of variants is crucial so that doctors can reference them and provide a diagnosis for patients with a genetic disorder.
鈥淪adly, many people, including my son, have not received the diagnosis they need which has difficult implications for them.
鈥淔or example without a diagnosis it can be very difficult to get a place at an appropriate school, or access desperately needed services.
鈥淚t鈥檚 galling to know that someone out there might have identified the variant which caused his illness, but may not have named it correctly so there鈥檚 no way of finding it.鈥�
He added: 鈥淰ariantValidator has been around for 7 years and is considered the gold standard in terms of naming genetic variants accurately so other clinicians will be able to find the definition and use them.
鈥淏ut in a vast number of cases that is just not happening because it鈥檚 easier and quicker to cut corners or rely on outdated systems only recognisable in specific clinical disciplines.
鈥淭he problem is so widespread I鈥檝e even come across experts responsible for setting clinical standards making these errors when naming variants in genetics focussed policy guidelines鈥�.
鈥淥ur work is with the Human genome, but the nomenclature of genetic variants in viruses and other pathogens are also similarly non-standardised - and that鈥檚 also a problem which needs to be addressed.
鈥淣omenclature should accurately describe the changes in DNA sequencing observed when there is a variant when compared to a standard sequence. But in many cases, this is simply not happening and is part of a complex set of problems that is causing miss or missed diagnoses.鈥�
The paper Standardising variant naming in literature with VariantValidator to increase diagnostic rates is available