Despite the identification of gene mutations in methyl CpG binding protein 2 (MECP2) being linked to Rett syndrome (RS), research has been hindered by the lack of commercially available reference materials.
Through collaboration between the Centers for Disease Control and Prevention (CDC) and members of the clinical-laboratory and non-profit–research communities, 35 DNA samples containing many common RS genetic variants have now been characterized and made publicly available, eliminating a major stumbling-block for investigators and opening the possibility of earlier, more accurate diagnosis of Rett syndrome, reports The Journal of Molecular Diagnostics.
The study was conducted via the CDC Genetic Testing Reference Materials Coordination Program (GeT-RM), which aims to help the genetic testing community obtain appropriate and well-defined reference materials for inherited genetic disorders, including cancer and infectious diseases. Researchers selected eight cell lines from RS patients already available from the National Institute of General Medical Sciences' Coriell Cell Repository, which contained six of the most common mutations that cause RS, as well as one additional point mutation. In addition, DNA was obtained from 27 newly established cell lines derived from blood samples from Rett patients, which included a number of other MECP2 variants. Two of the samples were from males.
The samples were sent for DNA sequence and deletion/duplication analyses (using MLPA, semi-quantitative PCR, or array) to College of American Pathologist–accredited clinical genetic testing laboratories, and each sample was tested in between two to five laboratories. The investigators found that the results were concordant among laboratories and assay platforms.
"The panel of 35 publicly available genomic DNA samples developed and characterized as part of this study contains a wide variety of point mutations, deletions, and duplications in both male and female samples that can be used by clinical laboratories to ensure the quality of Rett syndrome testing," asserts Dr. Kalman.
Point mutations or deletions/insertions of the MECP2 gene, which regulates aspects of brain development as well as the expression of other genes, were discovered to be associated with most cases of RS in 1999. However, since there are still no FDA-approved assays for Rett syndrome, laboratories have developed their own tests but need reference materials to standardize their techniques, validate assays, and meet regulatory and accreditation requirements. Ideally, the reference materials should be well characterized and contain the variants most commonly seen in RS patients.
"The availability of a renewable source of characterized reference materials for Rett syndrome will help to ensure the accuracy of these genetic tests and facilitate research and test development," comments Lisa Kalman, PhD, of the Division of Laboratory Programs, Standards, and Services at the Centers for Disease Control and Prevention.
"Molecular diagnosis of Rett syndrome is performed by examination of patient DNA for MECP2 mutations using a variety of molecular diagnostic methods," explains Dr. Kalman. "Genetic testing can help to confirm or establish the diagnosis of RS, especially when patients are young and the phenotype may not be completely apparent. Testing may also be important for at-risk relatives, prenatal diagnosis, or evaluation of an embryo prior to implantation during in vitro fertilization."
Rett syndrome, a dominant X-linked neurodevelopmental disorder that primarily affects girls, occurs in one of every 10,000 to 15,000 live births. Girls with RS first appear to grow and develop normally, but between the ages of 1 and 4 years start to exhibit development delays, loss of purposeful use of the hands, slowed brain and head growth, and motor difficulties. In later stages, affected individuals may develop a spectrum of symptoms with varying severity, including muscle weakness, rigidity, spasticity, abnormal posturing, inability to speak, seizures, and repetitive hand movements such as wringing or washing.
Eileen Leahy | EurekAlert!
Fiber optic biosensor-integrated microfluidic chip to detect glucose levels
29.04.2016 | The Optical Society
Got good fat?
27.04.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...
As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.
Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
29.04.2016 | Physics and Astronomy
29.04.2016 | Health and Medicine
29.04.2016 | Life Sciences