The study was conducted by Dr. Stephen W. Scherer from The Hospital for Sick Children (SickKids), Dr. Bridget Fernandez from Memorial University, and Dr. Kristiina Tammimies from the Centre of Neurodevelopment Disorders at Karolinska Institutet, Stockholm, Sweden. The study was published today in the Journal of the American Medical Association (JAMA).
The autism spectrum disorders are clinically and genetically diverse. The total number of genetic and genomic variations that confer ASD susceptibility is in the hundreds. Significant progress has been made over the past five years in identifying genetic changes that predispose a person to the development of ASD.
“We studied the DNA of 258 children from Newfoundland and Labrador using two relatively new forms of genome-wide testing, and we were interested in determining the proportion of children in whom we could find an ASD-associated genetic change,” said Fernandez, Professor and Chair of the Discipline of Genetics in the Faculty of Medicine. ” The two tests were chromosomal microarray (CMA) which is currently the first-line genetic test for children with ASD, and the second was whole exome sequencing (WES), which scans almost all of the coding parts of the genome to identify mutations.”
Fernandez explained that CMA has been used for over five years in genetic clinics, whereas WES is more commonly used in the research setting and has just been introduced into diagnostic laboratories.
Scherer, Director of The Centre for Applied Genomics and Senior Scientist at SickKids, and Director of the McLaughlin Centre at the University of Toronto, explained that this is the first study to look at the combined yield of both tests in a group of children who are typically found in the community.
“Our study is unique in that we examined a large cohort of children with Autism Spectrum Disorder (ASD) that were collected in a typical developmental paediatric clinic. Most other genetic studies in ASD studied groups of children/families that have some specific features, for example, two siblings being on the spectrum.”
The results of the study showed that overall, 16 per cent of the children with ASD had a positive result on one or both tests.
Also 20 per cent of the 258 children had a significant number of minor physical abnormalities (MPAs). One or two MPAs (for example a single palmar crease) are common in the general population, but when a child has multiple of these, it may be due to a genetic change that expressed itself when the child was in utero and that is also linked to the fact that the child went on to develop an ASD. The diagnostic yield of both tests was highest (35 per cent) in the children classified as having ‘complex ASD’ based on physical examination. The authors recommend that this group of children be prioritized for early genome-wide testing.
“In some cases, a positive test result alters a child’s medical management, for example we know that we should be watching for the development of obesity or diabetes because of the type of genetic change,” said Fernandez. “We expect the diagnostic rates to increase over the next several years as more laboratory data is collected from WES and whole genome sequencing (WGS). This should allow us to use genetic testing to make earlier diagnoses, which means earlier intervention and improved outcomes.”
The Hospital for Sick Children (SickKids)