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Martinez-Granero F, Blanco-Kelly F, Sanchez-Jimeno C, et al. Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders. NPJ Genom Med. 2021;6(1):25doi: 10.1038/s41525-021-00188-7.
Martinez-Granero, F., Blanco-Kelly, F., Sanchez-Jimeno, C., Avila-Fernandez, A., Arteche, A., Bustamante-Aragones, A., Rodilla, C., Rodríguez-Pinilla, E., Riveiro-Alvarez, R., Tahsin-Swafiri, S., Trujillo-Tiebas, M. J., Ayuso, C., Rodríguez de Alba, M., Lorda-Sanchez, I., & Almoguera, B. (2021). Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders. NPJ genomic medicine, 6(1), 25. https://doi.org/10.1038/s41525-021-00188-7
Martinez-Granero, Francisco, et al. "Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders." NPJ genomic medicine vol. 6,1 (2021): 25. doi: https://doi.org/10.1038/s41525-021-00188-7
Martinez-Granero F, Blanco-Kelly F, Sanchez-Jimeno C, Avila-Fernandez A, Arteche A, Bustamante-Aragones A, Rodilla C, Rodríguez-Pinilla E, Riveiro-Alvarez R, Tahsin-Swafiri S, Trujillo-Tiebas MJ, Ayuso C, Rodríguez de Alba M, Lorda-Sanchez I, Almoguera B. Comparison of the diagnostic yield of aCGH and genome-wide sequencing across different neurodevelopmental disorders. NPJ Genom Med. 2021 Mar 25;6(1):25. doi: 10.1038/s41525-021-00188-7. PMID: 33767182; PMCID: PMC7994713.
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NPJ Genom Med. 2021 Mar 25;6(1):25. doi: 10.1038/s41525-021-00188-7.

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

NPJ genomic medicine

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

Affiliations

  1. Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain.
  2. Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
  3. Department of Genetics, 12 de Octubre University Hospital, Madrid, Spain.
  4. Department of Genetics and Genomics, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain. [email protected].
  5. Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain. [email protected].

PMID: 33767182 PMCID: PMC7994713 DOI: 10.1038/s41525-021-00188-7

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.

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