Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases
Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Micr...
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| Veröffentlicht in: | PloS one 2007-03, Vol.2 (3), p.e327-e327 |
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| creator | Lu, Xinyan Shaw, Chad A Patel, Ankita Li, Jiangzhen Cooper, M Lance Wells, William R Sullivan, Cathy M Sahoo, Trilochan Yatsenko, Svetlana A Bacino, Carlos A Stankiewicz, Pawel Ou, Zhishu Chinault, A Craig Beaudet, Arthur L Lupski, James R Cheung, Sau W Ward, Patricia A |
| description | Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Microarray Analysis (CMA).
CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation. |
| doi_str_mv | 10.1371/journal.pone.0000327 |
| format | Article |
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CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0000327</identifier><identifier>PMID: 17389918</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Allelic Imbalance - genetics ; Chromosomes ; Chromosomes, Human - genetics ; Cloning ; Comparative Genomic Hybridization - methods ; Congenital diseases ; Copy number ; Cytogenetics ; Deoxyribonucleic acid ; Diagnostic systems ; DNA ; DNA microarrays ; Genes ; Genetic counseling ; Genetic screening ; Genetic Variation ; Genetics and Genomics/Cancer Genetics ; Genetics and Genomics/Chromosome Biology ; Genetics and Genomics/Complex Traits ; Genetics and Genomics/Epigenetics ; Genetics and Genomics/Gene Discovery ; Genetics and Genomics/Genetics of Disease ; Genome, Human ; Genomes ; Genomics ; Humans ; Hybridization ; Infant, Newborn ; Intellectual disabilities ; Karyotypes ; Karyotyping ; Laboratories ; Medical research ; Medicine ; Microarray Analysis - methods ; Oligonucleotide Array Sequence Analysis - methods ; Pathogenesis ; Patients ; Phenotype ; Physicians ; Reference Values</subject><ispartof>PloS one, 2007-03, Vol.2 (3), p.e327-e327</ispartof><rights>COPYRIGHT 2007 Public Library of Science</rights><rights>2007 Lu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Lu et al. 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c780t-a73ad60afcb031a3be0df66a95f0d84a0002c04b6deaf1d39be3151e2311f1b33</citedby><cites>FETCH-LOGICAL-c780t-a73ad60afcb031a3be0df66a95f0d84a0002c04b6deaf1d39be3151e2311f1b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828620/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828620/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17389918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Xinyan</creatorcontrib><creatorcontrib>Shaw, Chad A</creatorcontrib><creatorcontrib>Patel, Ankita</creatorcontrib><creatorcontrib>Li, Jiangzhen</creatorcontrib><creatorcontrib>Cooper, M Lance</creatorcontrib><creatorcontrib>Wells, William R</creatorcontrib><creatorcontrib>Sullivan, Cathy M</creatorcontrib><creatorcontrib>Sahoo, Trilochan</creatorcontrib><creatorcontrib>Yatsenko, Svetlana A</creatorcontrib><creatorcontrib>Bacino, Carlos A</creatorcontrib><creatorcontrib>Stankiewicz, Pawel</creatorcontrib><creatorcontrib>Ou, Zhishu</creatorcontrib><creatorcontrib>Chinault, A Craig</creatorcontrib><creatorcontrib>Beaudet, Arthur L</creatorcontrib><creatorcontrib>Lupski, James R</creatorcontrib><creatorcontrib>Cheung, Sau W</creatorcontrib><creatorcontrib>Ward, Patricia A</creatorcontrib><title>Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Microarray Analysis (CMA).
CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation.</description><subject>Allelic Imbalance - genetics</subject><subject>Chromosomes</subject><subject>Chromosomes, Human - genetics</subject><subject>Cloning</subject><subject>Comparative Genomic Hybridization - methods</subject><subject>Congenital diseases</subject><subject>Copy number</subject><subject>Cytogenetics</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnostic systems</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>Genes</subject><subject>Genetic counseling</subject><subject>Genetic screening</subject><subject>Genetic Variation</subject><subject>Genetics and Genomics/Cancer Genetics</subject><subject>Genetics and Genomics/Chromosome Biology</subject><subject>Genetics and Genomics/Complex Traits</subject><subject>Genetics and Genomics/Epigenetics</subject><subject>Genetics and Genomics/Gene Discovery</subject><subject>Genetics and Genomics/Genetics of Disease</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Infant, Newborn</subject><subject>Intellectual disabilities</subject><subject>Karyotypes</subject><subject>Karyotyping</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Microarray Analysis - methods</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Phenotype</subject><subject>Physicians</subject><subject>Reference Values</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUx4so7u7oNxAtCAs-zJiT9JL4ICyDl4GFBW8vPoTTNJ3JkDZj0orz7Td1qs6IC6YPCcnvnNP_uSTJEyALYCW83LrBd2gXO9fpBYmL0fJecg6C0XlBCbt_dD5LLkLYEpIzXhQPkzMoGRcC-HnydWlNZxTa1LQ7q1vd9dgb16WuSdXGu9YF18bX1ijv0Hvcpxij7oMJr9IwtC36_cjSHFi6c6HvsI-4wqDDo-RBgzbox9M-Sz6_ffNp-X5-ffNutby6nquSk36OJcO6INioijBAVmlSN0WBIm9IzTOM0qgiWVXUGhuomag0gxw0ZQANVIzNkmcHvzvrgpzyEiSInADJS07vJCgXAMDzkVgdiNrhVu68GYVJh0b-vHB-LdH3RlktaUlFVcToKKpMCIpMsFJlALTOVaaL6Ov1FG2oWl2rmFOP9sTp6UtnNnLtvkvglI_lmiWXkwPvvg069LI1QWlrsdNuCLKMeSIF5xF8_hf4b_V3U8cZWByoNUaRpmtc_DcVv1rH4scma0y8v8pKSnme5aPMFycGken1j36NQwhy9fHD_7M3X07ZyyN2o9H2m-DsMLZlOAWzAxhbMwSvm98pBiLHGfmlU44zIqcZiWZPj8vzx2gaCnYLp1IKtA</recordid><startdate>20070328</startdate><enddate>20070328</enddate><creator>Lu, Xinyan</creator><creator>Shaw, Chad A</creator><creator>Patel, Ankita</creator><creator>Li, Jiangzhen</creator><creator>Cooper, M Lance</creator><creator>Wells, William R</creator><creator>Sullivan, Cathy M</creator><creator>Sahoo, Trilochan</creator><creator>Yatsenko, Svetlana A</creator><creator>Bacino, Carlos A</creator><creator>Stankiewicz, Pawel</creator><creator>Ou, Zhishu</creator><creator>Chinault, A Craig</creator><creator>Beaudet, Arthur L</creator><creator>Lupski, James R</creator><creator>Cheung, Sau W</creator><creator>Ward, Patricia A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20070328</creationdate><title>Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases</title><author>Lu, Xinyan ; Shaw, Chad A ; Patel, Ankita ; Li, Jiangzhen ; Cooper, M Lance ; Wells, William R ; Sullivan, Cathy M ; Sahoo, Trilochan ; Yatsenko, Svetlana A ; Bacino, Carlos A ; Stankiewicz, Pawel ; Ou, Zhishu ; Chinault, A Craig ; Beaudet, Arthur L ; Lupski, James R ; Cheung, Sau W ; Ward, Patricia A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c780t-a73ad60afcb031a3be0df66a95f0d84a0002c04b6deaf1d39be3151e2311f1b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Allelic Imbalance - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Xinyan</au><au>Shaw, Chad A</au><au>Patel, Ankita</au><au>Li, Jiangzhen</au><au>Cooper, M Lance</au><au>Wells, William R</au><au>Sullivan, Cathy M</au><au>Sahoo, Trilochan</au><au>Yatsenko, Svetlana A</au><au>Bacino, Carlos A</au><au>Stankiewicz, Pawel</au><au>Ou, Zhishu</au><au>Chinault, A Craig</au><au>Beaudet, Arthur L</au><au>Lupski, James R</au><au>Cheung, Sau W</au><au>Ward, Patricia A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2007-03-28</date><risdate>2007</risdate><volume>2</volume><issue>3</issue><spage>e327</spage><epage>e327</epage><pages>e327-e327</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Array Comparative Genomic Hybridization (a-CGH) is a powerful molecular cytogenetic tool to detect genomic imbalances and study disease mechanism and pathogenesis. We report our experience with the clinical implementation of this high resolution human genome analysis, referred to as Chromosomal Microarray Analysis (CMA).
CMA was performed clinically on 2513 postnatal samples from patients referred with a variety of clinical phenotypes. The initial 775 samples were studied using CMA array version 4 and the remaining 1738 samples were analyzed with CMA version 5 containing expanded genomic coverage. Overall, CMA identified clinically relevant genomic imbalances in 8.5% of patients: 7.6% using V4 and 8.9% using V5. Among 117 cases referred for additional investigation of a known cytogenetically detectable rearrangement, CMA identified the majority (92.5%) of the genomic imbalances. Importantly, abnormal CMA findings were observed in 5.2% of patients (98/1872) with normal karyotypes/FISH results, and V5, with expanded genomic coverage, enabled a higher detection rate in this category than V4. For cases without cytogenetic results available, 8.0% (42/524) abnormal CMA results were detected; again, V5 demonstrated an increased ability to detect abnormality. Improved diagnostic potential of CMA is illustrated by 90 cases identified with 51 cryptic microdeletions and 39 predicted apparent reciprocal microduplications in 13 specific chromosomal regions associated with 11 known genomic disorders. In addition, CMA identified copy number variations (CNVs) of uncertain significance in 262 probands; however, parental studies usually facilitated clinical interpretation. Of these, 217 were interpreted as familial variants and 11 were determined to be de novo; the remaining 34 await parental studies to resolve the clinical significance.
This large set of clinical results demonstrates the significantly improved sensitivity of CMA for the detection of clinically relevant genomic imbalances and highlights the need for comprehensive genetic counseling to facilitate accurate clinical correlation and interpretation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>17389918</pmid><doi>10.1371/journal.pone.0000327</doi><tpages>e327</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2007-03, Vol.2 (3), p.e327-e327 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1950105782 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Allelic Imbalance - genetics Chromosomes Chromosomes, Human - genetics Cloning Comparative Genomic Hybridization - methods Congenital diseases Copy number Cytogenetics Deoxyribonucleic acid Diagnostic systems DNA DNA microarrays Genes Genetic counseling Genetic screening Genetic Variation Genetics and Genomics/Cancer Genetics Genetics and Genomics/Chromosome Biology Genetics and Genomics/Complex Traits Genetics and Genomics/Epigenetics Genetics and Genomics/Gene Discovery Genetics and Genomics/Genetics of Disease Genome, Human Genomes Genomics Humans Hybridization Infant, Newborn Intellectual disabilities Karyotypes Karyotyping Laboratories Medical research Medicine Microarray Analysis - methods Oligonucleotide Array Sequence Analysis - methods Pathogenesis Patients Phenotype Physicians Reference Values |
| title | Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases |
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