Novel Diagnostic Test Improving the Diagnosis of a Common Genetic Cause of Autism

Oct 29, 2019 | Autism, CNS, Fragile X Syndrome, Intellectual Disabilities

Novel Diagnostic Test Improving the Diagnosis of a Common Genetic Cause of Autism

The Murdoch Children’s Research Institute (MCRI) in collaboration with Lineagen, Inc., a Utah-based diagnostic genetic testing and clinical services information company, has produced a stand-alone test that can more precisely diagnose people with a common genetic disability and an autism spectrum disorder. They have put forth a more accurate and timely way to identify those with Fragile X syndrome, one of the most common causes of intellectual disability and an autism spectrum disorder.

Fragile X Syndrome Background

Affecting about 1 in 4,000 children, nearly 90,000 Australians and over one million Americans are impacted in some way. A large proportion of these are women who themselves are not affected with Fragile X, but carry a DNA ‘premutation’ in their FMR1 gene. This premutation predisposes these women to have children with Fragile X.

A major issue with Fragile X, reports the study sponsors in a recent press release, is that at a young age the syndrome is not clinically distinct, with an average diagnosis in Australia about five years, and according to the Centers for Disease Control and Prevention, over 3 years in America. Delayed diagnoses represent a real problem: affected children lack the medical care they would have needed in a timely manner. One family may have multiple affected children prior to diagnosing the first child.

There are considerable public and private costs associated with Fragile X with estimations as high as $2.5 million to the health system for raising one affected child.

Methylation Specific Quantitative Melt Analysis (MS-QMA)

The sponsors used a novel test called Methylation Specific Quantitative Melt Analysis (MS-QMA). A one-step process, the sponsors claim based on the most recent study that the results reveal a more accurate and timely diagnosis of Fragile X in those children that are affected and referred in for treatment for genetic testing.

The Study

Lineagen and MCRI compared DNA test results on more than 300 patients from pediatric clinics in the United States and Australia. These patients were known to either contain Fragile X mutations as detected by standard testing or no mutations detected by standard testing. While the second group of patients had no Fragile X mutations detected by standard CGG repeat testing, they were likewise diagnosed by physicians as having a form of intellectual disability with/or without autism.

All genetic testing was carried out in Associate Professor David Godler’s laboratory at MCRI using MS-QMA on make and female samples blinded by Lineagen. Once the blind was lifted, all male and female patients with known Fragile X diagnosis received correct diagnosis using MS-QMA. The study team also identified one additional female patient with a Fragile X full mutation in a small proportion of cells, which wasn’t detected by the standard two-step testing process.


During the study, the one-step test looks at the number of chemical modifications or “marks” called methylation, added to a patient’s FMR1 gene in Fragile X, which are not present in typically developing children without Fragile X syndrome. Increasing these marks reduces the production of a protein called FMRP required for healthy brain development and function. This study for the first time reveals that the number of these marks can be increased, even in people without the usual genetic changes seen in Fragile X syndrome (called CGG repeats). This is information heretofore not known, according to the sponsors, in part because current standard testing doesn’t involve reviewing these marks as part of the initial CGG screen.

The study team also identified smaller more common FMR1 alleles not typically tested for methylation (a tell-tale sign of Fragile X) exhibiting abnormal methylation signature in significant numbers of affected patients reported Professor Godler.

Murdoch Children’s Research Institute (MCRI)

MCRI is an Australian pediatric medical research institute located in Melbourne, Victoria affiliated with the Royal Children’s Hospital and the University of Melbourne. The institute has six research themes including cellular biology, clinical sciences, genetics, infection and immunity, population health and data science.

Who is Lineagen?

Lineagen is a Utah-based, privately-held personal genetic testing company. In operation since 2006, they have raised over $60 million. The company collaborated with two leading autism research institutions (University of Utah and the Children’s Hospital of Philadelphia—CHOP) to identify novel genetic variants likely causal of autism spectrum disorder. The Utah-based venture was granted an exclusive commercial license to these novel genetic variants. The markers originating from CHOP–published in Nature and PLoS Genetics—were named by TIME magazine as one of the top ten medical breakthroughs in 2009. 

Lineagen markets genetic laboratory services to healthcare providers and in 2012 they inked a deal with Affymetrix to secure exclusive rights to develop a proprietary chromosomal microarray assay based on Affymetrix’ GeneChip technology platform. 

With about 80 employees they are led by Michael Paul who has a Ph.D. from the University of Utah in Molecular Biology but also worked for periods in local Utah venture capital firms.

Other Contributors

In addition to Lineagen and MCRI, other participants in the study included the University of Melbourne, Victorian Genetic Services, Genetics of Learning Disability (Newcastle) and the Royal Children’s Hospital.

Lead Research/Investigator

Professor David Godler 

Call to Action: Interested in learning more if you are based in Australia consider connecting with MCRI and Professor Godler’s team and in the U.S. Lineagen. Need help? TrialSite News concierge service has helped hundreds make important connections since our inception in late 2018.

Source: PR Newswire


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