title: Characterization of patients referred for non-specific intellectual disability testing: the importance of autosomal genes for diagnosis.
abstract: Genetic testing for non-specific intellectual disability (ID) presents challenges in daily clinical practice. Historically, the focus of the genetic elucidation of non-specific ID has been on genes on the X chromosome, and recent research has brought attention to the growing contribution of autosomal genes. In addition, next-generation sequencing (NGS) has greatly improved the ability to simultaneously analyze multiple genetic loci, making large panel testing a practical approach to testing for non-specific ID. We performed NGS analysis of a total of 90 genes implicated in non-specific ID. The 90 genes included 56 X-linked genes and 34 autosomal genes. Pathogenic variants were identified in 11 of 52 (21%) patient samples. Nine of the eleven cases harbored mutations in autosomal genes including AP4B1, STXB1, SYNGAP1, TCF4 and UBE3A. Our mutation-positive cases provide further evidence supporting the prevalence of autosomal mutations in patients referred for non-specific ID testing and the utility of their inclusion in multi-gene panel analysis.
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Tan
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Topper
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: D
authors.initials: D
authors.lastname: Del Gaudio
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: V
authors.initials: V
authors.lastname: Nelakuditi
authors.affiliation: Division of Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Shchelochkov
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: M J M
authors.initials: MJM
authors.lastname: Nowaczyk
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Zeesman
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Brady
authors.affiliation: Department of Medical Genetics, Montreal General Hospital, Montreal, QC, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Russell
authors.affiliation: Department of Pediatrics, Section of Genetics, University of Colorado, Aurora, CO, USA.
authors.forename: N
authors.initials: N
authors.lastname: Meeks
authors.affiliation: Division of Genetic and Metabolic Disorders, Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sastry
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Arndt
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: F
authors.initials: F
authors.lastname: Kobiernicki
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Shaw
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Das
keywords: X-linked chromosome; autosomal; intellectual disability; next-generation sequencing; non-specific