title: Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders.
abstract: Copy number variants (CNVs) detected by chromosomal microarray analysis (CMA) significantly contribute to understanding the etiology of autism spectrum disorder (ASD) and other related conditions. In recognition of the value of CMA testing and its impact on medical management, CMA is in medical guidelines as a first-tier test in the evaluation of children with these disorders. As CMA becomes adopted into routine care for these patients, it becomes increasingly important to report these clinical findings. This study summarizes the results of over 4 years of CMA testing by a CLIA-certified clinical testing laboratory. Using a 2.8 million probe microarray optimized for the detection of CNVs associated with neurodevelopmental disorders, we report an overall CNV detection rate of 28.1% in 10,351 consecutive patients, which rises to nearly 33% in cases without ASD, with only developmental delay/intellectual disability (DD/ID) and/or multiple congenital anomalies (MCA). The overall detection rate for individuals with ASD is also significant at 24.4%. The detection rate and pathogenic yield of CMA vary significantly with the indications for testing, age, and gender, as well as the specialty of the ordering doctor. We note discrete differences in the most common recurrent CNVs found in individuals with or without a diagnosis of ASD.
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. kho@lineagen.com.|Department of Pediatrics, University of Utah, Salt Lake City, UT 84132, USA. kho@lineagen.com.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Ho
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. bwassman@lineagen.com.
authors.forename: E Robert
authors.initials: ER
authors.lastname: Wassman
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. abaxter@lineagen.com.
authors.forename: Adrianne L
authors.initials: AL
authors.lastname: Baxter
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. chensel@lineagen.com.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Hensel
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. mmartin@lineagen.com.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Martin
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. aprasad@lineagen.com.
authors.forename: Aparna
authors.initials: A
authors.lastname: Prasad
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. htwede@lineagen.com.
authors.forename: Hope
authors.initials: H
authors.lastname: Twede
authors.affiliation: Lineagen, Inc., Salt Lake City, UT 84109, USA. rvanzo@lineagen.com.
authors.forename: Rena J
authors.initials: RJ
authors.lastname: Vanzo
authors.affiliation: Departments of Psychiatry, Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, UT 66160, USA. mbutler4@kumc.edu.
authors.forename: Merlin G
authors.initials: MG
authors.lastname: Butler
mesh_terms: D000067877:Autism Spectrum Disorder / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008297:Male; D046228:Microarray Analysis
keywords: FirstStepDx PLUS; autism spectrum disorder; chromosomal microarray; copy number variants; neurodevelopmental disorders; variants of unknown significance