Cognitive deficit and autism spectrum disorders: Prospective diagnosis by array CGH

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, Array Referral Consortium, Kathryn FriendSharon M. Bain, Sui Yu, Kym Abbott, Sonny Bata, Yolanda Benard, J. Bethell, Drago Bratkovic, Yumin Chan, V. Chong, Richard Cockington, Maria Concepcion, Brian Conway, D. Corlis, Samuel Crafter, Mary Cossick, Liz Coventry, Luke Eckersley, Phil Egan, Gareth Forster, Liberty Gallus, Sanjay Gehlot, Damien Gilby, C. Goodall, Andrew Grieve, Shahid Haque, Tom Han, Afdal Ibrahim, Amita Ingole, Judy Jaensch, Deepa Jeyaseelan, A. Katdare, Stephen Klaric, Daniel Kritzinger, Christopher Lamb, Paul Lang, Sonja Latzel, Diana Lawrence, Christine Lee, Kathy Lee, Kerrie MacDonald, Paul Machet, Suja Mathew, Preveena Nair, Khurram Noori, Josephine Nozza, Michael Nugent, Nadine Ogle, M. O'Keefe, Greg Pallas, P. Parry, Chris Pearson, P. Petek, T. Pouras, Rick Power, Clair Pridmore, Patrick Quinn, Kavita Rasiah, Nicholas Ricci, James Rice, Michael Smiley, J. Smith, William Staridas, N. Stewart, Wakinyjan Tabart, Mark Thesinger, David Thomas, Reji Thomas, Suzanna Thompson, Andrew Tidemann, Con Tsourtos, Sonali Vasilunas, Colin Whyatt, Mandy Yiu

Research output: Contribution to journalReview article

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)41-45
Number of pages5
JournalPathology
Volume46
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

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Comparative Genomic Hybridization
Intellectual Disability
Cytogenetics
Genetic Services
Diagnostic Services
Disease Susceptibility
Genetic Counseling
Aneuploidy
Epilepsy
Autism Spectrum Disorder

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Nicholl, J., Waters, W., Mulley, J. C., Suwalski, S., Brown, S., Hull, Y., ... Yiu, M. (2014). Cognitive deficit and autism spectrum disorders: Prospective diagnosis by array CGH. Pathology, 46(1), 41-45. https://doi.org/10.1097/PAT.0000000000000043
Nicholl, Jillian ; Waters, Wendy ; Mulley, John C. ; Suwalski, Shanna ; Brown, Sue ; Hull, Yvonne ; Barnett, Christopher ; Haan, Eric ; Thompson, Elizabeth M. ; Liebelt, Jan ; Mcgregor, Lesley ; Harbord, Michael G. ; Entwistle, John ; Munt, Chris ; White, Dierdre ; Chitti, Anthony ; Baulderstone, David ; Ketteridge, David ; Consortium, Array Referral ; Friend, Kathryn ; Bain, Sharon M. ; Yu, Sui ; Abbott, Kym ; Bata, Sonny ; Benard, Yolanda ; Bethell, J. ; Bratkovic, Drago ; Chan, Yumin ; Chong, V. ; Cockington, Richard ; Concepcion, Maria ; Conway, Brian ; Corlis, D. ; Crafter, Samuel ; Cossick, Mary ; Coventry, Liz ; Eckersley, Luke ; Egan, Phil ; Forster, Gareth ; Gallus, Liberty ; Gehlot, Sanjay ; Gilby, Damien ; Goodall, C. ; Grieve, Andrew ; Haque, Shahid ; Han, Tom ; Ibrahim, Afdal ; Ingole, Amita ; Jaensch, Judy ; Jeyaseelan, Deepa ; Katdare, A. ; Klaric, Stephen ; Kritzinger, Daniel ; Lamb, Christopher ; Lang, Paul ; Latzel, Sonja ; Lawrence, Diana ; Lee, Christine ; Lee, Kathy ; MacDonald, Kerrie ; Machet, Paul ; Mathew, Suja ; Nair, Preveena ; Noori, Khurram ; Nozza, Josephine ; Nugent, Michael ; Ogle, Nadine ; O'Keefe, M. ; Pallas, Greg ; Parry, P. ; Pearson, Chris ; Petek, P. ; Pouras, T. ; Power, Rick ; Pridmore, Clair ; Quinn, Patrick ; Rasiah, Kavita ; Ricci, Nicholas ; Rice, James ; Smiley, Michael ; Smith, J. ; Staridas, William ; Stewart, N. ; Tabart, Wakinyjan ; Thesinger, Mark ; Thomas, David ; Thomas, Reji ; Thompson, Suzanna ; Tidemann, Andrew ; Tsourtos, Con ; Vasilunas, Sonali ; Whyatt, Colin ; Yiu, Mandy. / Cognitive deficit and autism spectrum disorders : Prospective diagnosis by array CGH. In: Pathology. 2014 ; Vol. 46, No. 1. pp. 41-45.
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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.",
author = "Jillian Nicholl and Wendy Waters and Mulley, {John C.} and Shanna Suwalski and Sue Brown and Yvonne Hull and Christopher Barnett and Eric Haan and Thompson, {Elizabeth M.} and Jan Liebelt and Lesley Mcgregor and Harbord, {Michael G.} and John Entwistle and Chris Munt and Dierdre White and Anthony Chitti and David Baulderstone and David Ketteridge and Consortium, {Array Referral} and Kathryn Friend and Bain, {Sharon M.} and Sui Yu and Kym Abbott and Sonny Bata and Yolanda Benard and J. Bethell and Drago Bratkovic and Yumin Chan and V. Chong and Richard Cockington and Maria Concepcion and Brian Conway and D. Corlis and Samuel Crafter and Mary Cossick and Liz Coventry and Luke Eckersley and Phil Egan and Gareth Forster and Liberty Gallus and Sanjay Gehlot and Damien Gilby and C. Goodall and Andrew Grieve and Shahid Haque and Tom Han and Afdal Ibrahim and Amita Ingole and Judy Jaensch and Deepa Jeyaseelan and A. Katdare and Stephen Klaric and Daniel Kritzinger and Christopher Lamb and Paul Lang and Sonja Latzel and Diana Lawrence and Christine Lee and Kathy Lee and Kerrie MacDonald and Paul Machet and Suja Mathew and Preveena Nair and Khurram Noori and Josephine Nozza and Michael Nugent and Nadine Ogle and M. O'Keefe and Greg Pallas and P. Parry and Chris Pearson and P. Petek and T. Pouras and Rick Power and Clair Pridmore and Patrick Quinn and Kavita Rasiah and Nicholas Ricci and James Rice and Michael Smiley and J. Smith and William Staridas and N. Stewart and Wakinyjan Tabart and Mark Thesinger and David Thomas and Reji Thomas and Suzanna Thompson and Andrew Tidemann and Con Tsourtos and Sonali Vasilunas and Colin Whyatt and Mandy Yiu",
year = "2014",
doi = "10.1097/PAT.0000000000000043",
language = "English",
volume = "46",
pages = "41--45",
journal = "Pathology",
issn = "0031-3025",
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Nicholl, J, Waters, W, Mulley, JC, Suwalski, S, Brown, S, Hull, Y, Barnett, C, Haan, E, Thompson, EM, Liebelt, J, Mcgregor, L, Harbord, MG, Entwistle, J, Munt, C, White, D, Chitti, A, Baulderstone, D, Ketteridge, D, Consortium, AR, Friend, K, Bain, SM, Yu, S, Abbott, K, Bata, S, Benard, Y, Bethell, J, Bratkovic, D, Chan, Y, Chong, V, Cockington, R, Concepcion, M, Conway, B, Corlis, D, Crafter, S, Cossick, M, Coventry, L, Eckersley, L, Egan, P, Forster, G, Gallus, L, Gehlot, S, Gilby, D, Goodall, C, Grieve, A, Haque, S, Han, T, Ibrahim, A, Ingole, A, Jaensch, J, Jeyaseelan, D, Katdare, A, Klaric, S, Kritzinger, D, Lamb, C, Lang, P, Latzel, S, Lawrence, D, Lee, C, Lee, K, MacDonald, K, Machet, P, Mathew, S, Nair, P, Noori, K, Nozza, J, Nugent, M, Ogle, N, O'Keefe, M, Pallas, G, Parry, P, Pearson, C, Petek, P, Pouras, T, Power, R, Pridmore, C, Quinn, P, Rasiah, K, Ricci, N, Rice, J, Smiley, M, Smith, J, Staridas, W, Stewart, N, Tabart, W, Thesinger, M, Thomas, D, Thomas, R, Thompson, S, Tidemann, A, Tsourtos, C, Vasilunas, S, Whyatt, C & Yiu, M 2014, 'Cognitive deficit and autism spectrum disorders: Prospective diagnosis by array CGH', Pathology, vol. 46, no. 1, pp. 41-45. https://doi.org/10.1097/PAT.0000000000000043

Cognitive deficit and autism spectrum disorders : Prospective diagnosis by array CGH. / Nicholl, Jillian; Waters, Wendy; Mulley, John C.; Suwalski, Shanna; Brown, Sue; Hull, Yvonne; Barnett, Christopher; Haan, Eric; Thompson, Elizabeth M.; Liebelt, Jan; Mcgregor, Lesley; Harbord, Michael G.; Entwistle, John; Munt, Chris; White, Dierdre; Chitti, Anthony; Baulderstone, David; Ketteridge, David; Consortium, Array Referral; Friend, Kathryn; Bain, Sharon M.; Yu, Sui; Abbott, Kym; Bata, Sonny; Benard, Yolanda; Bethell, J.; Bratkovic, Drago; Chan, Yumin; Chong, V.; Cockington, Richard; Concepcion, Maria; Conway, Brian; Corlis, D.; Crafter, Samuel; Cossick, Mary; Coventry, Liz; Eckersley, Luke; Egan, Phil; Forster, Gareth; Gallus, Liberty; Gehlot, Sanjay; Gilby, Damien; Goodall, C.; Grieve, Andrew; Haque, Shahid; Han, Tom; Ibrahim, Afdal; Ingole, Amita; Jaensch, Judy; Jeyaseelan, Deepa; Katdare, A.; Klaric, Stephen; Kritzinger, Daniel; Lamb, Christopher; Lang, Paul; Latzel, Sonja; Lawrence, Diana; Lee, Christine; Lee, Kathy; MacDonald, Kerrie; Machet, Paul; Mathew, Suja; Nair, Preveena; Noori, Khurram; Nozza, Josephine; Nugent, Michael; Ogle, Nadine; O'Keefe, M.; Pallas, Greg; Parry, P.; Pearson, Chris; Petek, P.; Pouras, T.; Power, Rick; Pridmore, Clair; Quinn, Patrick; Rasiah, Kavita; Ricci, Nicholas; Rice, James; Smiley, Michael; Smith, J.; Staridas, William; Stewart, N.; Tabart, Wakinyjan; Thesinger, Mark; Thomas, David; Thomas, Reji; Thompson, Suzanna; Tidemann, Andrew; Tsourtos, Con; Vasilunas, Sonali; Whyatt, Colin; Yiu, Mandy.

In: Pathology, Vol. 46, No. 1, 2014, p. 41-45.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Cognitive deficit and autism spectrum disorders

T2 - Prospective diagnosis by array CGH

AU - Nicholl, Jillian

AU - Waters, Wendy

AU - Mulley, John C.

AU - Suwalski, Shanna

AU - Brown, Sue

AU - Hull, Yvonne

AU - Barnett, Christopher

AU - Haan, Eric

AU - Thompson, Elizabeth M.

AU - Liebelt, Jan

AU - Mcgregor, Lesley

AU - Harbord, Michael G.

AU - Entwistle, John

AU - Munt, Chris

AU - White, Dierdre

AU - Chitti, Anthony

AU - Baulderstone, David

AU - Ketteridge, David

AU - Consortium, Array Referral

AU - Friend, Kathryn

AU - Bain, Sharon M.

AU - Yu, Sui

AU - Abbott, Kym

AU - Bata, Sonny

AU - Benard, Yolanda

AU - Bethell, J.

AU - Bratkovic, Drago

AU - Chan, Yumin

AU - Chong, V.

AU - Cockington, Richard

AU - Concepcion, Maria

AU - Conway, Brian

AU - Corlis, D.

AU - Crafter, Samuel

AU - Cossick, Mary

AU - Coventry, Liz

AU - Eckersley, Luke

AU - Egan, Phil

AU - Forster, Gareth

AU - Gallus, Liberty

AU - Gehlot, Sanjay

AU - Gilby, Damien

AU - Goodall, C.

AU - Grieve, Andrew

AU - Haque, Shahid

AU - Han, Tom

AU - Ibrahim, Afdal

AU - Ingole, Amita

AU - Jaensch, Judy

AU - Jeyaseelan, Deepa

AU - Katdare, A.

AU - Klaric, Stephen

AU - Kritzinger, Daniel

AU - Lamb, Christopher

AU - Lang, Paul

AU - Latzel, Sonja

AU - Lawrence, Diana

AU - Lee, Christine

AU - Lee, Kathy

AU - MacDonald, Kerrie

AU - Machet, Paul

AU - Mathew, Suja

AU - Nair, Preveena

AU - Noori, Khurram

AU - Nozza, Josephine

AU - Nugent, Michael

AU - Ogle, Nadine

AU - O'Keefe, M.

AU - Pallas, Greg

AU - Parry, P.

AU - Pearson, Chris

AU - Petek, P.

AU - Pouras, T.

AU - Power, Rick

AU - Pridmore, Clair

AU - Quinn, Patrick

AU - Rasiah, Kavita

AU - Ricci, Nicholas

AU - Rice, James

AU - Smiley, Michael

AU - Smith, J.

AU - Staridas, William

AU - Stewart, N.

AU - Tabart, Wakinyjan

AU - Thesinger, Mark

AU - Thomas, David

AU - Thomas, Reji

AU - Thompson, Suzanna

AU - Tidemann, Andrew

AU - Tsourtos, Con

AU - Vasilunas, Sonali

AU - Whyatt, Colin

AU - Yiu, Mandy

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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U2 - 10.1097/PAT.0000000000000043

DO - 10.1097/PAT.0000000000000043

M3 - Review article

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