Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability
Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics. We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS...
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| Veröffentlicht in: | Genetics in medicine 2022-11, Vol.24 (11), p.2296-2307 |
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| creator | Lindstrand, Anna Ek, Marlene Kvarnung, Malin Anderlid, Britt-Marie Björck, Erik Carlsten, Jonas Eisfeldt, Jesper Grigelioniene, Giedre Gustavsson, Peter Hammarsjö, Anna Helgadóttir, Hafdís T. Hellström-Pigg, Maritta Kuchinskaya, Ekaterina Lagerstedt-Robinson, Kristina Levin, Lars-Åke Lieden, Agne Lindelöf, Hillevi Malmgren, Helena Nilsson, Daniel Svensson, Eva Paucar, Martin Sahlin, Ellika Tesi, Bianca Tham, Emma Winberg, Johanna Winerdal, Max Wincent, Josephine Johansson Soller, Maria Pettersson, Maria Nordgren, Ann |
| description | Individuals with intellectual disability (ID) and/or neurodevelopment disorders (NDDs) are currently investigated with several different approaches in clinical genetic diagnostics.
We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421).
The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed.
Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.
[Display omitted] |
| doi_str_mv | 10.1016/j.gim.2022.07.022 |
| format | Article |
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We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421).
The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed.
Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.
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We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421).
The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed.
Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.
[Display omitted]</description><subject>Chromosomal microarray</subject><subject>Clinical diagnostics</subject><subject>FMR1 analysis</subject><subject>Genome sequencing</subject><subject>Intellectual disability</subject><issn>1098-3600</issn><issn>1530-0366</issn><issn>1530-0366</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>D8T</sourceid><recordid>eNp9kU9P3DAQxaOqlaC0H4Cbj1ySjpOsE6snRMsfCYkL9Go59mQ722y82M4ivn1ntYgjpxk__d5Ifq8oziVUEqT6sanWtK1qqOsKuorHp-JUrhoooVHqM--g-7JRACfF15Q2ALJrajgt8AbnsEWR8HnB2dG8FpSE5fecKNMexUgx5XKiGUXGlEUOwpNdzyGhoNnTnvxipyReKP9lIeM0ocssMZbsQBPl12_Fl5EZ_P42z4qn69-PV7fl_cPN3dXlfenaVufSoh5Hq5R1HdpV6533rfOy96tRN4MeB9-PUqpagxo6p5Tre9CuH2wjcWCuOSvK4930grtlMLtIWxtfTbBk3qR_vKFpVxLaj_lf9OfShLg2Ey1GatnoA39x5HcxcF4pmy0lxz-2M4YlmbrjnJWWcEDlEXUxpBRxfD8uwRwqMxvDlZlDZQY6w4M9P48e5Iz2hNEkR9wKeoqcqfGBPnD_B90Loo4</recordid><startdate>20221101</startdate><enddate>20221101</enddate><creator>Lindstrand, Anna</creator><creator>Ek, Marlene</creator><creator>Kvarnung, Malin</creator><creator>Anderlid, Britt-Marie</creator><creator>Björck, Erik</creator><creator>Carlsten, Jonas</creator><creator>Eisfeldt, Jesper</creator><creator>Grigelioniene, Giedre</creator><creator>Gustavsson, Peter</creator><creator>Hammarsjö, Anna</creator><creator>Helgadóttir, Hafdís T.</creator><creator>Hellström-Pigg, Maritta</creator><creator>Kuchinskaya, Ekaterina</creator><creator>Lagerstedt-Robinson, Kristina</creator><creator>Levin, Lars-Åke</creator><creator>Lieden, Agne</creator><creator>Lindelöf, Hillevi</creator><creator>Malmgren, Helena</creator><creator>Nilsson, Daniel</creator><creator>Svensson, Eva</creator><creator>Paucar, Martin</creator><creator>Sahlin, Ellika</creator><creator>Tesi, Bianca</creator><creator>Tham, Emma</creator><creator>Winberg, Johanna</creator><creator>Winerdal, Max</creator><creator>Wincent, Josephine</creator><creator>Johansson Soller, Maria</creator><creator>Pettersson, Maria</creator><creator>Nordgren, Ann</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>ABXSW</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>DG8</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0003-0806-5602</orcidid></search><sort><creationdate>20221101</creationdate><title>Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability</title><author>Lindstrand, Anna ; 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We compared the results from 3 diagnostic pipelines in patients with ID/NDD: genome sequencing (GS) first (N = 100), GS as a secondary test (N = 129), or chromosomal microarray (CMA) with or without FMR1 analysis (N = 421).
The diagnostic yield was 35% (GS-first), 26% (GS as a secondary test), and 11% (CMA/FMR1). Notably, the age of diagnosis was delayed by 1 year when GS was performed as a secondary test and the cost per diagnosed individual was 36% lower with GS first than with CMA/FMR1. Furthermore, 91% of those with a negative result after CMA/FMR1 analysis (338 individuals) have not yet been referred for additional genetic testing and remain undiagnosed.
Our findings strongly suggest that genome analysis outperforms other testing strategies and should replace traditional CMA and FMR1 analysis as a first-line genetic test in individuals with ID/NDD. GS is a sensitive, time- and cost-effective method that results in a confirmed molecular diagnosis in 35% of all referred patients.
[Display omitted]</abstract><pub>Elsevier Inc</pub><doi>10.1016/j.gim.2022.07.022</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-0806-5602</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1098-3600 |
| ispartof | Genetics in medicine, 2022-11, Vol.24 (11), p.2296-2307 |
| issn | 1098-3600 1530-0366 1530-0366 |
| language | eng |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Alma/SFX Local Collection |
| subjects | Chromosomal microarray Clinical diagnostics FMR1 analysis Genome sequencing Intellectual disability |
| title | Genome sequencing is a sensitive first-line test to diagnose individuals with intellectual disability |
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