Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders

Abstract Most consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnost...

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Autores principales:	Francisco Martinez-Granero, Fiona Blanco-Kelly, Carolina Sanchez-Jimeno, Almudena Avila-Fernandez, Ana Arteche, Ana Bustamante-Aragones, Cristina Rodilla, Elvira Rodríguez-Pinilla, Rosa Riveiro-Alvarez, Saoud Tahsin-Swafiri, Maria Jose Trujillo-Tiebas, Carmen Ayuso, Marta Rodríguez de Alba, Isabel Lorda-Sanchez, Berta Almoguera
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/60825b0a88124fa993f8c183177a345c
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spelling	oai:doaj.org-article:60825b0a88124fa993f8c183177a345c2021-12-02T17:03:51ZComparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders10.1038/s41525-021-00188-72056-7944https://doaj.org/article/60825b0a88124fa993f8c183177a345c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00188-7https://doaj.org/toc/2056-7944Abstract Most consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and other NDDs. These categories were further subclassified based on the most frequent accompanying signs and symptoms into isolated forms, forms with epilepsy; forms with micro/macrocephaly and syndromic forms. Two hundred and forty-five patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no additional cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results suggest that NGS could be used as a first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.Francisco Martinez-GraneroFiona Blanco-KellyCarolina Sanchez-JimenoAlmudena Avila-FernandezAna ArtecheAna Bustamante-AragonesCristina RodillaElvira Rodríguez-PinillaRosa Riveiro-AlvarezSaoud Tahsin-SwafiriMaria Jose Trujillo-TiebasCarmen AyusoMarta Rodríguez de AlbaIsabel Lorda-SanchezBerta AlmogueraNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Francisco Martinez-Granero Fiona Blanco-Kelly Carolina Sanchez-Jimeno Almudena Avila-Fernandez Ana Arteche Ana Bustamante-Aragones Cristina Rodilla Elvira Rodríguez-Pinilla Rosa Riveiro-Alvarez Saoud Tahsin-Swafiri Maria Jose Trujillo-Tiebas Carmen Ayuso Marta Rodríguez de Alba Isabel Lorda-Sanchez Berta Almoguera Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
description	Abstract Most consensus recommendations for the genetic diagnosis of neurodevelopmental disorders (NDDs) do not include the use of next generation sequencing (NGS) and are still based on chromosomal microarrays, such as comparative genomic hybridization array (aCGH). This study compares the diagnostic yield obtained by aCGH and clinical exome sequencing in NDD globally and its spectrum of disorders. To that end, 1412 patients clinically diagnosed with NDDs and studied with aCGH were classified into phenotype categories: global developmental delay/intellectual disability (GDD/ID); autism spectrum disorder (ASD); and other NDDs. These categories were further subclassified based on the most frequent accompanying signs and symptoms into isolated forms, forms with epilepsy; forms with micro/macrocephaly and syndromic forms. Two hundred and forty-five patients of the 1412 were subjected to clinical exome sequencing. Diagnostic yield of aCGH and clinical exome sequencing, expressed as the number of solved cases, was compared for each phenotype category and subcategory. Clinical exome sequencing was superior than aCGH for all cases except for isolated ASD, with no additional cases solved by NGS. Globally, clinical exome sequencing solved 20% of cases (versus 5.7% by aCGH) and the diagnostic yield was highest for all forms of GDD/ID and lowest for Other NDDs (7.1% versus 1.4% by aCGH) and ASD (6.1% versus 3% by aCGH). In the majority of cases, diagnostic yield was higher in the phenotype subcategories than in the mother category. These results suggest that NGS could be used as a first-tier test in the diagnostic algorithm of all NDDs followed by aCGH when necessary.
format	article
author	Francisco Martinez-Granero Fiona Blanco-Kelly Carolina Sanchez-Jimeno Almudena Avila-Fernandez Ana Arteche Ana Bustamante-Aragones Cristina Rodilla Elvira Rodríguez-Pinilla Rosa Riveiro-Alvarez Saoud Tahsin-Swafiri Maria Jose Trujillo-Tiebas Carmen Ayuso Marta Rodríguez de Alba Isabel Lorda-Sanchez Berta Almoguera
author_facet	Francisco Martinez-Granero Fiona Blanco-Kelly Carolina Sanchez-Jimeno Almudena Avila-Fernandez Ana Arteche Ana Bustamante-Aragones Cristina Rodilla Elvira Rodríguez-Pinilla Rosa Riveiro-Alvarez Saoud Tahsin-Swafiri Maria Jose Trujillo-Tiebas Carmen Ayuso Marta Rodríguez de Alba Isabel Lorda-Sanchez Berta Almoguera
author_sort	Francisco Martinez-Granero
title	Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
title_short	Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
title_full	Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
title_fullStr	Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
title_full_unstemmed	Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders
title_sort	comparison of the diagnostic yield of acgh and genome-wide sequencing across different neurodevelopmental disorders
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/60825b0a88124fa993f8c183177a345c
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Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders

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