Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A better genetic test for autism

15.03.2010
In largest study to date, chromosomal microarray analysis picks up more abnormalities than current tests

A large study from Children's Hospital Boston and the Boston-based Autism Consortium finds that a genetic test that samples the entire genome, known as chromosomal microarray analysis, has about three times the detection rate for genetic changes related to autism spectrum disorders (ASDs) than standard tests. Publishing in the April issue of Pediatrics (and online March 15), the authors urge that CMA become part of the first-line genetic work-up for ASDs.

Expectant parents who have family members with ASDs, as well as families who already have an affected child, often request genetic testing. However, there is still only limited knowledge about actual causative genes. The currently recommended tests (karyotyping to look for chromosomal abnormalities and testing for Fragile X, the single largest known genetic cause of ASDs) often come up negative. Chromosomal microarray analysis (CMA) is a genome-wide assay that examines the chromosomes for tiny, sub-microscopic deletions or duplications of DNA sequences, known as copy-number variants.

CMA offers about 100-fold greater resolution than standard karyotyping. However, since it is new, it is often considered a second-tier test. Depending on where a person lives, or what insurance they have, CMA may not be covered by health insurance. "Based on our findings, CMA should be considered as part of the initial clinical diagnostic evaluation of patients with ASDs," says Bai-Lin Wu, PhD, Director of Children's DNA Diagnostic Lab in the Department of Laboratory Medicine, which has offered CMA to families since 2006.

The research team, led by co-senior authors Wu (heading the Children's team), and David Miller, MD, PhD, of Children's Division of Genetics and Department of Laboratory Medicine (heading the Autism Consortium team), assessed the diagnostic value of CMA in the largest cohort to date -- 933 patients with a clinical diagnosis of ASD (by DSM-IV-TR criteria) who received clinical genetic testing in 2006, 2007 and 2008.

Half were Children's patients who had their samples submitted to the hospital's DNA Diagnostic Laboratory, and the others were recruited through the Autism Consortium, a research and clinical collaboration of five Boston-area medical centers. Nearly half of the patients were diagnosed with autistic disorder, nearly half with PDD-NOS (pervasive developmental disorder – not otherwise specified) and about 3 percent with Asperger disorder. Ages ranged from 13 months to 22 years.

Testing included the two currently used tests (G-banded karyotype and fragile X), as well as CMA. When the researchers compared the tests' diagnostic yield, they found:

Karyotyping yielded abnormal results in 2.23 percent of patients
Fragile X testing was abnormal in 0.46 percent
CMA results were judged to be abnormal in 7.3 percent of patients when the entire length of the chromosomes (the whole genome) was sampled.

Extrapolating from these results, the researchers estimate that without CMA, genetic diagnosis will be missed in at least 5 percent of ASD cases. CMA performed best in certain subgroups, such as girls with autistic disorder, and past studies indicate that it also has a higher yield in patients with intellectual disability (who constituted only 12 percent of this sample).

"CMA clearly detects more abnormalities than other genetic tests that have been the standard of care for many years," says Miller. "We're hoping this evidence will convince insurance companies to cover this testing universally."

In all, roughly 15 percent of people with autism have a known genetic cause. Establishing a clear genetic diagnosis helps families obtain early intervention and services for autism, and helps parents predict the possibility of having another child with autism.

In addition, by pinpointing bits of chromosomes that are deleted or duplicated, CMA can help researchers zero in on specific causative genes within that stretch of DNA. They can also begin to classify patients according to the type of deletion or duplication they have, and try to find specific treatment approaches for each sub-type of autism.

"Just in the last two years, a number of studies have revealed the clinical importance of ever smaller chromosome deletions and duplications found with advanced microarray technology," says Wu. "These new, highly-efficient tests can help in the evaluation or confirmation of autism spectrum disorders and other developmental disorders, leading to early diagnosis and intervention and a significantly improved developmental outcome."

Two known chromosome locations – on chromosome 16 (16p11.2) and chromosome 15 (15q13.2q13.3) accounted for 17 percent of abnormal CMA findings. Both chromosome abnormalities were initially linked with ASDs by Children's Hospital Boston and collaborators in The New England Journal of Medicine and the Journal of Medical Genetics, respectively, in 2008. Children's now offers specific tests targeting both of these "hot spots."

However, the researchers note that most copy-number changes were unique or identified in only a small number of patients, so their implications need further study. Many of them are presumed to be related to ASDs because they involve important genes, cover a large region of the chromosome, or because the child is the first person in that family to have the change.

"Some deletions and duplications are rare and specific to one individual or one family," says Miller. "Learning about them is going to be an evolving process. There won't be one single test that finds all genetic changes related to autism, until we completely understand the entire genome."

The paper's co-first authors were Autism Consortium members Yiping Shen, PhD, of Children's Department of Laboratory Medicine and the Center for Human Genetic Research at Massachusetts General Hospital, and Kira Dies, ScM, LGC, of the Family Research Network of the Autism Consortium and Children's Multi-Disciplinary Tuberous Sclerosis Program. A number of specialists from Children's Departments of Neurology, Developmental Medicine and Clinical Genetics and physicians from other medical centers in greater Boston were also authors on the study. The research was supported by the Nancy Lurie Marks Family Foundation, the Simons Foundation, Autism Speaks and the National Institutes of Health.

Families interested in scheduling an appointment at Children's may call the Developmental Medicine Center (617-355-7025) or the Department of Neurology (617-355-2711).

Citation: Shen Y; et al. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics 2010 Apr; 125(4):e1-e17. (Published online March 15)

Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 13 members of the Institute of Medicine and 12 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.

Keri Stedman | EurekAlert!
Further information:
http://www.childrens.harvard.edu

More articles from Studies and Analyses:

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>