Étude de validité analytique et clinique de FirstStepDx PLUS: une biopuce chromosomique optimisée pour les patients avec des troubles du développement neurologique

Aperçu: G.M.

L'analyse de biopuce chromosomique (CMA) est reconnue comme le test de premier niveau dans l'évaluation génétique des enfants présentant des retards de développement, des troubles intellectuels, des anomalies congénitales et des troubles du spectre de l'autisme d'étiologie inconnue.

L'étude propose des données démontrant la validité analytique et clinique de FSDX et fournit un aperçu des résultats des 7 500 premiers patients consécutifs testés cliniquement.

Il est en outre démontré que l'échantillonnage buccal est une méthode efficace d'obtention d'échantillons d'ADN, ce qui peut fournir des résultats améliorés par rapport à l'échantillonnage sanguin traditionnel chez les patients souffrant de troubles neurodéveloppementaux.

Cliquer ICI pour accéder à l'intégralité de l'article en anglais

PLoS Curr. 2017 Feb 27;9. pii: ecurrents.eogt.7d92ce775800ef3fbc72e3840fb1bc22. doi: 10.1371/currents.eogt.7d92ce775800ef3fbc72e3840fb1bc22.

Analytical and Clinical Validity Study of FirstStepDx PLUS: A Chromosomal Microarray Optimized for Patients with Neurodevelopmental Conditions

Hensel C¹, Vanzo R², Martin M¹, Dixon S³, Lambert C⁴, Levy B⁵, Nelson L⁶, Peiffer A⁷, Ho KS⁷, Rushton P¹, Serrano M¹, South S⁸, Ward K⁶, Wassman E¹.

Author information

1

Lineagen, Inc., Salt Lake City, Utah, USA.

2

Clinical Genetic Services, Lineagen, Inc., Salt Lake City, Utah, USA.

3

Operations, Lineagen, Inc., Salt Lake City, Utah, USA.

4

Department of Internal Medicine, Center for Global Health, Division of Translational Informatics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

5

Department of Pathology & Cell Biology, Columbia University Medical Center, New York, New York, USA.

6

Affiliated Genetics Laboratory, Inc., Salt Lake City, Utah, USA.

7

Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA; Lineagen, Inc., Salt Lake City, Utah, USA.

8

ARUP Laboratories, Salt Lake City, Utah, USA; 23andMe, Inc., Mountain View, California, USA.

Abstract

INTRODUCTION:

Chromosomal microarray analysis (CMA) is recognized as the first-tier test in the genetic evaluation of children with developmental delays, intellectual disabilities, congenital anomalies and autism spectrum disorders of unknown etiology.

ARRAY DESIGN:

To optimize detection of clinically relevant copy number variants associated with these conditions, we designed a whole-genome microarray, FirstStep^Dx PLUS (FSDX). A set of 88,435 custom probes was added to the Affymetrix CytoScanHD platform targeting genomic regions strongly associated with these conditions. This combination of 2,784,985 total probes results in the highest probe coverage and clinical yield for these disorders.

RESULTS AND DISCUSSION:

Clinical testing of this patient population is validated on DNA from either non-invasive buccal swabs or traditional blood samples. In this report we provide data demonstrating the analytic and clinical validity of FSDX and provide an overview of results from the first 7,570 consecutive patients tested clinically. We further demonstrate that buccal sampling is an effective method of obtaining DNA samples, which may provide improved results compared to traditional blood sampling for patients with neurodevelopmental disorders who exhibit somatic mosaicism.

PMID: 28357155

PMCID: PMC5346028

DOI: 10.1371/currents.eogt.7d92ce775800ef3fbc72e3840fb1bc22