title: Cognitive deficit and autism spectrum disorders: prospective diagnosis by array CGH.
abstract: The aim of this study was to determine prospectively the frequency of pathogenic chromosomal microdeletions and microduplications in a large group of referred patients with developmental delay (DD), intellectual disability (ID) or autism spectrum disorders (ASD) within a genetic diagnostic service. First tier testing was applied using a standardised oligo-array comparative genomic hybridization (CGH) platform, replacing conventional cytogenetic testing that would have been used in the past. Copy number variants (CNVs) found to be responsible for the clinical condition on the request form could all be subdivided into three groups: well established pathogenic microdeletion/microduplication/aneuploidy syndromes, predicted pathogenic CNVs as interpreted by the laboratory, and recently established pathogenic disease susceptibility CNVs. Totalled from these three groups, with CNVs of uncertain significance excluded, detection rates were: DD (13.0%), ID (15.6%), ASD (2.3%), ASD with DD (8.2%), ASD with ID (12.7%) and unexplained epilepsy with DD, ID and ASD (10.9%). The greater diagnostic sensitivity arising from routine application of array CGH, compared with previously used conventional cytogenetics, outweighs the interpretative issues for the reporting laboratory and referring clinician arising from detection of CNVs of uncertain significance. Precise determination of any previously hidden molecular defect responsible for the patient's condition is translated to improved genetic counselling.
authors.affiliation: 1Cytogenetics, Department of Genetic Medicine, Directorate of Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, North Adelaide 2Molecular Genetics, Department of Genetic Medicine, Directorate of Genetics and Molecular Pathology, SA Pathology at Women's and Children's Hospital, North Adelaide 3School of Molecular and Biomedical Sciences, The University of Adelaide 4School of Paediatrics and Reproductive Health, The University of Adelaide 5South Australian Clinical Genetics Service, SA Pathology at Women's and Children's Hospital, North Adelaide 6Centre for Disability Health, North East Clinic, Modbury Hospital, Adelaide 7Ashford Medical Centre, Ashford, Adelaide 8Flinders Medical Centre, Bedford Park 9Calvary Hospital, North Adelaide 10Women's and Children's Health Network, North Adelaide 11Parks Community Health Service, Angle Park, South Australia, Australia 12see Acknowledgements for all members.
authors.forename: Jillian
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authors.lastname: Nicholl
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authors.lastname: Suwalski
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authors.lastname: Baulderstone
authors.forename: David
authors.initials: D
authors.lastname: Ketteridge
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authors.lastname: Friend
authors.forename: Sharon M
authors.initials: SM
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authors.forename: Sui
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mesh_terms: D001315:Australia; D002659:Child Development Disorders, Pervasive / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D004827:Epilepsy / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D020440:Gene Duplication; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D011446:Prospective Studies; D017384:Sequence Deletion