title: Targeted NGS meets expert clinical characterization: Efficient diagnosis of spastic paraplegia type 11.
abstract: Next generation sequencing (NGS) is transforming the diagnostic approach for neurological disorders, since it allows simultaneous analysis of hundreds of genes, even based on just a broad, syndromic patient categorization. However, such an approach bears a high risk of incidental and uncertain genetic findings. We report a patient with spastic paraplegia whose comprehensive neurological and imaging examination raised a high clinical suspicion of SPG11. Thus, although our NGS pipeline for this group of disorders includes gene panel and exome sequencing, in this sample only the spatacsin gene region was captured and subsequently searched for mutations. Two probably pathogenic variants were quickly and clearly identified, confirming the diagnosis of SPG11. This case illustrates how combination of expert clinical characterization with highly oriented NGS protocols leads to a fast, cost-efficient diagnosis, minimizing the risk of findings with unclear significance.
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Castro-Fernández
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Servicio de Neurología, Complejo Hospitalario de Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Blanco-Arias
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Fundación Pública Galega de Medicina Xenómica, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Santomé-Collazo
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Amigo
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Spain; Center of Excellence in Genomic Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Carracedo
authors.affiliation: Instituto de Investigación Sanitaria de Santiago-IDIS, Spain; Grupo de Medicina Xenómica, CIBERER, Universidade de Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Spain.
authors.forename: Maria-Jesús
authors.initials: MJ
authors.lastname: Sobrido
keywords: Diagnosis; Hereditary spastic paraplegia; SPG11; Targeted NGS; Thin corpus callosum