Corporate Banner
Satellite Banner
Molecular & Clinical Diagnostics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Exome Sequencing: Potential Diagnostic Assay for Unexplained Intellectual Disability

Published: Monday, November 12, 2012
Last Updated: Monday, November 12, 2012
Bookmark and Share
Research findings confirming that de novo mutations represent a major cause of previously unexplained intellectual disability were presented at the American Society of Human Genetics 2012 meeting.

Josep de Ligt, M.Sc., bioinformatician and Ph.D. student in human genetics at Radboud University Nijmegen Medical Centre in The Netherlands, also reported findings lending support to the use of exome sequencing, which deciphers over 21,000 protein-coding genes and not the entire human genome, as a diagnostic assay to determine whether one or more genetic mutations explain a patient’s intellectual disability.

The cause of intellectual disability, which represents a wide range of phenotypes, or observable biological characteristics, is unknown in at least 50% of patients. Most individuals with intellectual disability without a known cause are the only members of their families with the condition. Because the cause of their child’s cognitive impairment is unknown, parents are often baffled.

The child with a cognitive disability is often an “isolated case without family history of the condition,” said de Ligt, adding that intellectual disability occurs in about 1% of the population.

By exome sequencing of 100 patients with unexplained cognitive impairment, de Ligt and his colleagues uncovered 79 genes with unique de novo mutations. These de novo mutations were present in the DNA of the patients but not in that of their parents whose exomes also were sequenced.

“All de novo as well as X-linked mutations identified in this study were interpreted in the context of the clinical diagnosis,” de Ligt pointed out. The diagnostic interpretation revealed that 16 of the 100 mutations were causative, or pathogenic. Ten of these mutations occurred in genes already known to be involved in intellectual disability, and three X-linked maternally-inherited mutations were identified.

In addition, de novo mutations were uncovered in three novel candidate genes, which after follow-up were found to be more frequently mutated in patients with intellectual disability.

“Comparison of these patients showed clear overlapping phenotypes, thereby establishing pathogenicity for these three new genes,” said de Ligt.

Furthermore, disruptive de novo mutations were identified in 19 additional genes with a functional link to intellectual disability. Because 19 genes were found in only a single patient, de Ligt said that a conclusive diagnosis based on these findings could not be made.

Additional studies in larger patient cohorts will likely to confirm a considerable proportion of these as true intellectual disability genes, raising the diagnostic yield of this approach, he added.

“This study confirms that de novo mutations represent a major cause of previously unexplained intellectual disability,” said Joris Veltman, Ph.D., associate professor in human genetics, Radboud University Nijmegen Medical Centre. “Because of the availability of large scale sequencing strategies, these mutations can now be readily revealed.”

de Ligt said that the results of the study recommend “exome sequencing as a diagnostic assay for patients with unexplained intellectual disability.”

The researchers’ abstract is titled, “Diagnostic exome sequencing in patients with intellectual disability of unknown cause.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,900+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
CDC Updates Zika Recommendations
CDC has issued updated Zika recommendations and guidance for healthcare providers with a focus on sexual transmission.
Review of the Analysis of Haemoglobin A1c for Diabetes Diagnostics
This paper aims to clarify methods, units, quality requirements, reference and cutoff limits for hemoglobin A1c (HbA1c) and ratio of blood glucose/HbA1c on the basis of the results from Finnish quality control surveys by comparing them to the literature.
Colon Cancer Blocked in Mice
Case Western Reserve University Researchers block common type of colon cancer tumour in mice, laying groundwork for human clinical trial.
Drug - Gene 'One-Two' Punch Against Cancer
Researchers identify gene-drug combinations that, together, target and kill cancer cells while not targeting healthy cells.
Liquid Biopsies Treating Ovarian Cancer
Researchers have discovered a promising monitor and treat recurrence of ovarian cancer. Detecting cancer long before tumours reappear.
72% Rise in Metastatic Prostate Cancer
Over the 2003-2013 period metastatic cancer has increased by an average of 72%, this could be caused by lax screening, more aggressive disease or both.
Lab-Tested Diagnosis Needed When Treating Persistent Diarrhea
New PCR multiplex method makes lab testing more effective.
Biomarker for Multiple Sclerosis Detection Discovered
Winthrop-University Hospital researchers discover biomarker for multiple sclerosis detection.
Scientists Link Bipolar Disorder to Unexpected Brain Region
Researchers from The Scripps Research Institute have found that gene within the brain’s striatum could be linked to biopolar disorder.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!