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Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10

BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients ar...

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Autores principales: Mak, Annisa Shui Lam, Chiu, Annie Ting Gee, Leung, Gordon Ka Chun, Mak, Christopher Chun Yu, Chu, Yoyo Wing Yiu, Mok, Gary Tsz Kin, Tang, Wing Fai, Chan, Kelvin Yuen Kwong, Tang, Mary Hoi Yin, Lau Yim, Elizabeth Tak-Kwong, So, Kin Wai, Tao, Victoria Qinchen, Fung, Cheuk Wing, Wong, Virginia Chun Nei, Uddin, Mohammed, Lee, So Lun, Marshall, Christian R., Scherer, Stephen W., Kan, Anita Sik Yau, Chung, Brian Hon Yin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485587/
https://www.ncbi.nlm.nih.gov/pubmed/28670437
http://dx.doi.org/10.1186/s13229-017-0136-x
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author Mak, Annisa Shui Lam
Chiu, Annie Ting Gee
Leung, Gordon Ka Chun
Mak, Christopher Chun Yu
Chu, Yoyo Wing Yiu
Mok, Gary Tsz Kin
Tang, Wing Fai
Chan, Kelvin Yuen Kwong
Tang, Mary Hoi Yin
Lau Yim, Elizabeth Tak-Kwong
So, Kin Wai
Tao, Victoria Qinchen
Fung, Cheuk Wing
Wong, Virginia Chun Nei
Uddin, Mohammed
Lee, So Lun
Marshall, Christian R.
Scherer, Stephen W.
Kan, Anita Sik Yau
Chung, Brian Hon Yin
author_facet Mak, Annisa Shui Lam
Chiu, Annie Ting Gee
Leung, Gordon Ka Chun
Mak, Christopher Chun Yu
Chu, Yoyo Wing Yiu
Mok, Gary Tsz Kin
Tang, Wing Fai
Chan, Kelvin Yuen Kwong
Tang, Mary Hoi Yin
Lau Yim, Elizabeth Tak-Kwong
So, Kin Wai
Tao, Victoria Qinchen
Fung, Cheuk Wing
Wong, Virginia Chun Nei
Uddin, Mohammed
Lee, So Lun
Marshall, Christian R.
Scherer, Stephen W.
Kan, Anita Sik Yau
Chung, Brian Hon Yin
author_sort Mak, Annisa Shui Lam
collection PubMed
description BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3′ exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-017-0136-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-54855872017-06-30 Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10 Mak, Annisa Shui Lam Chiu, Annie Ting Gee Leung, Gordon Ka Chun Mak, Christopher Chun Yu Chu, Yoyo Wing Yiu Mok, Gary Tsz Kin Tang, Wing Fai Chan, Kelvin Yuen Kwong Tang, Mary Hoi Yin Lau Yim, Elizabeth Tak-Kwong So, Kin Wai Tao, Victoria Qinchen Fung, Cheuk Wing Wong, Virginia Chun Nei Uddin, Mohammed Lee, So Lun Marshall, Christian R. Scherer, Stephen W. Kan, Anita Sik Yau Chung, Brian Hon Yin Mol Autism Research BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3′ exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13229-017-0136-x) contains supplementary material, which is available to authorized users. BioMed Central 2017-06-26 /pmc/articles/PMC5485587/ /pubmed/28670437 http://dx.doi.org/10.1186/s13229-017-0136-x Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Mak, Annisa Shui Lam
Chiu, Annie Ting Gee
Leung, Gordon Ka Chun
Mak, Christopher Chun Yu
Chu, Yoyo Wing Yiu
Mok, Gary Tsz Kin
Tang, Wing Fai
Chan, Kelvin Yuen Kwong
Tang, Mary Hoi Yin
Lau Yim, Elizabeth Tak-Kwong
So, Kin Wai
Tao, Victoria Qinchen
Fung, Cheuk Wing
Wong, Virginia Chun Nei
Uddin, Mohammed
Lee, So Lun
Marshall, Christian R.
Scherer, Stephen W.
Kan, Anita Sik Yau
Chung, Brian Hon Yin
Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10
title Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10
title_full Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10
title_fullStr Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10
title_full_unstemmed Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10
title_short Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10
title_sort use of clinical chromosomal microarray in chinese patients with autism spectrum disorder—implications of a copy number variation involving dpp10
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485587/
https://www.ncbi.nlm.nih.gov/pubmed/28670437
http://dx.doi.org/10.1186/s13229-017-0136-x
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