Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization.
Agatha SchlüterAgustín Rodriguez-PalmeroEdgard VerduraValentina Vélez-SantamaríaMontserrat RuizStéphane FourcadeLaura Planas-SerraJuan José MartínezCristina GuileraMarisa GirósRafael ArtuchMaría Eugenia YoldiMar O'CallaghanÁngeles García-CazorlaJudith ArmstrongItxaso MartiElisabet Mondragón RezolaClaire RedinJean Louis MandelDavid ConejoConcepción Sierra-CórcolesSergi BeltránMarta GutElida VázquezMireia Del ToroMónica TroncosoLuis A Pérez-JuradoLuis G Gutiérrez-SolanaAdolfo López de MunainCarlos CasasnovasSergio Aguilera-AlbesaAlfons MacayaAurora Pujolnull nullPublished in: Neurology (2022)
Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance.