Cognitive deficit and autism spectrum disorders: prospective diagnosis by array CGH.

Authors

• Jillian Nicholl
• Wendy Waters
• John C Mulley
• Shanna Suwalski
• Sue Brown
• Yvonne Hull
• Christopher Barnett
• Eric Haan
• Elizabeth M Thompson
• Jan Liebelt
• Lesley Mcgregor
• Michael G Harbord
• John Entwistle
• Chris Munt
• Dierdre White
• Anthony Chitti
• David Baulderstone
• David Ketteridge
• Kathryn Friend
• Sharon M Bain
• Sui Yu

Publication/Presentation Date

1-1-2014

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.

Volume

46

Issue

1

First Page

41

Last Page

45

ISSN

1465-3931

Published In/Presented At

Nicholl, J., Waters, W., Mulley, J. C., Suwalski, S., Brown, S., Hull, Y., Barnett, C., Haan, E., Thompson, E. M., Liebelt, J., Mcgregor, L., Harbord, M. G., Entwistle, J., Munt, C., White, D., Chitti, A., Baulderstone, D., Ketteridge, D., Array Referral Consortium, Friend, K., … Yu, S. (2014). Cognitive deficit and autism spectrum disorders: prospective diagnosis by array CGH. Pathology, 46(1), 41–45. https://doi.org/10.1097/PAT.0000000000000043

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

24300712

Department(s)

Administration and Leadership

Document Type

Article