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A new test improves the diagnosis of a common genetic cause of autism

URBAN SEA SALT. October 28, 2019 / PRNewswire / –

Research at a glance:

  • A new DNA test for fragile X syndrome has been shown to have accuracy and specificity approaching 100 percent
  • This is the first study that showed efficacy in female and male children with intellectual disability and / or autism of unknown genetic nature directed for testing in United States
  • Fragile X syndrome is one of the most common genetic causes of intellectual disability and autism spectrum disorders

A new stand-alone test can more accurately diagnose people with the typical genetic cause of autism than the current test system.

An international study conducted by Murdoch Children & # 39; s Research Institute (MCRI) in cooperation with Lineagen, Inc., an innovative company dealing with diagnostic genetic testing and clinical information services based in Utah, published in scientific reports, describes an attempt at a more cost-effective, accurate and timely way to identify people with fragile X syndrome, one of the most common genetic causes of intellectual disability and the autism spectrum.

The costs associated with X instability associated with raising one sick child were estimated at over USD 2.5 million to the healthcare system. *

Fragile X affects approximately 1 in 4,000 children from approximately 90,000 Australians and over a million Americans in some way. A large part of them are women who are not affected by Fragile X themselves, but have a "premutation" of DNA in the FMR1 gene. This premutation predisposes these women to having children with Fragile X.

The main problem with Fragile X is that at a young age the syndrome is not clinically pronounced and the average age of diagnosis in Australia about five years and, according to Centers for Disease Control and Prevention, over three three years in the US.

As a result of delayed diagnosis, sick children do not receive the medical care they need in a timely manner, and families may have many affected children before they receive a diagnosis for their first child.

Chief researcher Associate Professor MCRI David Godler they said families who have "premutation" carriers may have the option of having children without influence if they give timely advice on alternative reproductive options.

"The impact of delayed diagnosis is significant and can potentially be prevented not only by families but also by our healthcare system," he said.

"That's why we've developed our new test, called methylation-specific quantitative analysis (MS-QMA). It is a one-step process that helps in more accurate and faster diagnosis of Fragile X in sick children referred for genetic testing. "

A one-step test checks the number of chemical modifications or 'signs', called methylation, added to the patient's FMR1 gene in Fragile X that do not occur in typically developing children without Fragile X syndrome. Increasing these signs reduces the production of a protein called FMRP required for healthy development and functioning the brain. This study shows for the first time that the number of these signs can be increased, even in people without the usual genetic changes observed in fragile X syndrome (called CGG repeats). This has not been known until now, partly because the current standard tests do not require looking at these characters as part of the initial CGG screen.

Current standard testing tests these signs with a second separate test and only on a limited number of patients suspected of having a typical genetic change (CGG repeat) associated with Fragile X, called the full mutation and "large" permutation alleles. One reason for this is that this second methylation test is too expensive to be used to test all patients originally suspected of fragility X, and therefore some patients affected by Fragile X remain undetected.

In this study, Lineagen and MCRI compared the results of a DNA test on over 300 patients from children's clinics in United States and Australia. These patients were either found to contain fragile X chromosome mutations detected in standard tests or no mutations were detected in standard tests. While in the second group of patients no fragile X chromosome mutation was detected during standard CGG repeat tests, doctors also diagnosed them as intellectual disability with or without autism.

All genetic tests were carried out in the laboratory of Professor Godler at MCRI using MS-QMA on samples of men and women blinded by Lineagen. After raising the blinds, all male and female patients with known diagnosis of fragile X chromosome received the correct diagnosis using MS-QMA. The study also identified one additional patient with the full Fragile X mutation in a small proportion of cells that was not detected in a standard two-step test process.

"We also identified, for the first time, smaller, more common FMR1 alleles that are not normally tested for methylation (Fragile X warning sign) that had abnormal methylation signatures in a significant number of affected patients," Associate Professor Godler said.

"These abnormal signatures have been confirmed in the current standard confirmatory methylation test performed by Lineagen. These signatures can impair FMR1 gene function and potentially lead to clinical features similar to Fragile X, and is an active research area for my group. "

Lineagen CEO Dr Michael Paul he said, even after a series of the best possible clinical genetic tests, almost half of children with autism spectrum disorders do not receive a genetic diagnosis, so everything we can do to improve genetic diagnostic precision is important for families and their children.

Dr. Paul also said: "We are pleased that we were able to work with Associate Professor Golder and his team to identify up to 15 percent more patients with fragile X syndrome than is currently disclosed in the current study paradigm, which includes CGG FMR1 repeat analysis – Linear X fragility testing currently being performed on children suspected of being ill. "

"Lineagen's mission is to provide more accurate and precise genetic diagnoses of neurodevelopmental disorders in children faster, so this is a community we need to help and a challenge that we cannot ignore."

Researchers at Lineagen Inc in Utah. University of Melbourne, Victorian clinical genetics services, genetics learning difficulties in Newcastle, and the Royal Children's Hospital also contributed to these findings.

Publication: Charles H. Hensel. Rena J. Vanzo. Megan M. Martin. Ling ling. Solange M. Aliaga. Minh Bui. David I. Francis. Hope Twede. Mike H. Field. Jonathon W. Morison. David J. Amor and David E. Godler. "Abnormally methylated FMR1 in the absence of a detectable full mutation in USA A patient cohort directed to the study of fragile X chromosome, "Scientific reports. DOI: 10.1038 / s41598-019-51618-7

Available for the interview:

  • Associate Professor David Godler
  • Michael S. PaulDoctor, CEO and President, Lineagen

Murdoch Children & # 39; s Research Institute (MCRI) is the largest child health research institute in Australia involved in discovering and developing treatment methods to improve the health of children and adolescents in Australia and all over the world. They are pioneers of new methods of treatment, testing better vaccines and improving ways to diagnose and help sick children, children and adolescents. This is one of the few research institutes in the Australia offering genetic tests to find answers for families of children with previously undiagnosed conditions.

Contact with the media:
Byrne Bridie
Communication Specialist MCRI +613 9936 6211/0427 836 176

About Lineagen
Lineagen helps families and their healthcare providers get access to high-quality genetic testing to help personalize medical management for people with autism spectrum disorder (ASD) and other neurodevelopmental disorders. Lineagen's services are designed specifically for these families, which include DNA collection through a cheek swab, comprehensive reimbursement support and access to licensed / certified genetic consultants for all services rendered. The doctor's recommended genetic testing options include deletion / duplication, fragile X syndrome testing, whole exome and whole genome sequencing, and pharmacogenomic testing. Lineagen also strives to accelerate the diagnostic process, which is why we offer m-chat.org to help examine children at risk of ASD, and a telehealth platform via MyDevelopingChild, which allows families to access genetic tests from a comfortable home. Lineagen has been providing genetic testing services to families and their providers for over nine years and has performed over 60,000 tests for people with neurodevelopmental problems. Details: www.lineagen.com.

Contact with the media:
Calvin Chan, Lineagen Director of Marketing

  • The study was funded by the Victoria Government operational infrastructure support program, Murdoch Children & # 39; s Research Institute, Royal Children & # 39; s Hospital Foundation, Martin & E.H. Flack Trust, Pierce Armstrong Trust, Children's Financial Markets Foundation (Australia) (FMFC; grant number: 2017-361), National Health and Medical Research Council (NHMRC; grant numbers for the project: 104299 and 1103389 for D.E.G.) and Lineagen. D.E.G. the salary was also supported by the Next Generation Clinical Research Program – a career development scholarship financed by the Medical Research Future Fund (grant number 1141334). Megan Martin. Rena Vanzo. Hope Twede, and Charles Hensel were employees of Lineagen Inc. (commercial company) and received funding and share options from Lineagen Inc.

* Hollingsworth B, Harris A. Economic assessment of prenatal population screening for fragile X syndrome. Genet community. , 2005; 8 (2): 68–72

SOURCE Lineagen, Inc.

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