Analysis of genetic variation in the exome, the DNA sequence of genes that are translated into protein, can aid in uncovering the cause of conditions for which no genetic cause could previously be found, and this can directly impact clinical management, the annual conference of the European Society of Human Genetics will hear today.
Dr Jayne Hehir-Kwa, Assistant Professor of Bioinformatics in the Translational Research group, Department of Human Genetics, Radboud UMC, Nijmegen, The Netherlands, will describe results from her group's study that set out to determine whether copy number variants (CNVs), large genomic deletions or duplications, can contribute to diseases other than intellectual disability.
The role of CNVs in intellectual disability is well known, but their implication in other conditions is less so. "There are, for example, case reports describing deletions in blindness, but no-one has determined the full extent of CNVs in other patient groups," Dr Hehir-Kwa will say.
The team screened 600 patients for which no diagnosis or causal mutation could be found using current whole exome sequencing (WES) methodology, and looked genome-wide for a causal deletion or duplication. It is, they say, the first time anyone has screened systematically for a disease mechanism in such a large and diverse patient group, including five heterogeneous conditions – intellectual disability, deafness, blindness, metabolic disorders, and movement disorders.
"For these patient groups, targeted gene approaches have been traditionally used for mutation screening and hence the contribution of CNVs to these disease groups has never been established and genome-wide testing rarely applied," says Dr Hehir-Kwa. "Our results show that CNVs are a relatively common, clinically-relevant event."
CNVs were found in patients with many different kinds of disorders, for example retinitis pigmentosa (blindness), Usher syndrome (deafness), Bethlem/Ulrich myopathy (a congenital form of muscular dystrophy), hypotonia-cystinuria syndrome (a neonatal-onset metabolic disorder) and X-linked immunodeficiency (an inherited disorder of the immune system).
"Although WES is not perfect in terms of completely cataloguing genomic variation, our work has shown that it can play an important part in diagnosis. In addition to helping us devise better clinical management strategies for patients, it also affects their prognosis and provides information which can aid us with reproductive counselling for affected individuals," says Dr Hehir-Kwa. "As a result, we are now offering the CNV screening performed in our study as a standard diagnostic procedure in exome analysis for patients where the genetic cause of their condition has not been found previously."
The diagnostic yield differs between the different disease categories, the researchers say. Traditional screening for genetic mutations can explain 27% of intellectual disability, 52% of blindness, and up to 20% of individuals with mitochondrial and movement disorders. "This means that between 48-80% of patients screened with WES are not given a genetic diagnosis. By looking for CNVs in the exon regions of these undiagnosed patients we estimate that we can find such a diagnosis in about a further four percent.
In particular, the blindness conditions seem to have the highest yield of CNVs – up to seven percent," says Dr Hehir-Kwa. "I would like to see screening for more types of genomic variants become standard procedure in genetic diagnostics. The genome of an individual can contain all kinds of different variants, in all shapes and sizes, and it is important that we take all these variations into account." WES, when offered as a first tier diagnostic test, can give a high diagnostic yield, and the result is faster diagnostics at lower cost.
"The more complete and thorough we can make such a diagnostic test, the more accessible we make genetic testing for the public. However, clinical health care professionals need to be well informed about the different genetic disease mechanisms to provide the best possible counselling for patients," Dr Hehir-Kwa will conclude.
Mary Rice | Eurek Alert!
Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University
Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Life Sciences
17.10.2017 | Earth Sciences