Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders
- 16 August 2011
- journal article
- research article
- Published by Wiley in American Journal of Medical Genetics Part A
- Vol. 155 (10), 2386-2396
- https://doi.org/10.1002/ajmg.a.34177
Abstract
Recent studies suggest that copy number variations (CNVs) encompassing several genes involved in neurodevelopmental pathways are associated with a variety of neuropsychiatric phenotypes, including developmental delay (DD), mental retardation (MR), and autism spectrum disorders (ASDs). Here we present eight patients in a cohort of ∼1,200 patients referred for clinical array CGH testing for various neurodevelopmental phenotypes, who were identified to carry small (NFIA at 1p31.3, MEF2C at 5q14.3, and CAMAT1 at 1p36.23p36.31), neuron-specific splicing factor genes (RBFOX1 at 16p13.2p13.3), genes involved in synapse formation and maintenance (CNTNAP2 at 7q35 and LRFN5 at 14q21.2), and genes involved in neurotransmission (CHRNA7 at 15q13.3 and IL1RAPL1 at Xp21.2p21.3). Our report expands the list of neurodevelopmental genes deleted in various neurobehavioral phenotypes, expands the phenotypes caused by haploinsufficiency of previously reported critical neurodevelopmental genes, and elucidates the clinical relevance and need for careful clinical interpretation of some small CNVs <500 kb. This report also suggests that small clinically relevant deletions encompassing critical synaptic and other neurodevelopmental genes can present clinically with various neurobehavioral phenotypes, which implies the existence of overlapping neuronal pathways in the pathogenesis of these phenotypes.Keywords
This publication has 50 references indexed in Scilit:
- Functional impact of global rare copy number variation in autism spectrum disordersNature, 2010
- Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophreniaMolecular Psychiatry, 2010
- Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital AnomaliesAmerican Journal of Human Genetics, 2010
- Recurrent Rearrangements in Synaptic and Neurodevelopmental Genes and Shared Biologic Pathways in Schizophrenia, Autism, and Mental RetardationArchives of General Psychiatry, 2009
- Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genesMolecular Psychiatry, 2009
- Novel Submicroscopic Chromosomal Abnormalities Detected in Autism Spectrum DisorderBiological Psychiatry, 2008
- Structural Variation of Chromosomes in Autism Spectrum DisorderAmerican Journal of Human Genetics, 2008
- Molecular Cytogenetic Analysis and Resequencing of Contactin Associated Protein-Like 2 in Autism Spectrum DisordersAmerican Journal of Human Genetics, 2008
- Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disordersNature Genetics, 2006
- Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autismNature Genetics, 2003