RT Journal Article
T1 Expanding the Clinical and Genetic Spectra of Primary Immunodeficiency-Related Disorders With Clinical Exome Sequencing: Expected and Unexpected Findings.
A1 Rudilla, Francesc
A1 Franco-Jarava, Clara
A1 Martínez-Gallo, Mónica
A1 Garcia-Prat, Marina
A1 Martín-Nalda, Andrea
A1 Rivière, Jacques
A1 Aguiló-Cucurull, Aina
A1 Mongay, Laura
A1 Vidal, Francisco
A1 Solanich, Xavier
A1 Irastorza, Iñaki
A1 Santos-Pérez, Juan Luis
A1 Tercedor Sánchez, Jesús
A1 Cuscó, Ivon
A1 Serra, Clara
A1 Baz-Redón, Noelia
A1 Fernández-Cancio, Mónica
A1 Carreras, Carmen
A1 Vagace, José Manuel
A1 Garcia-Patos, Vicenç
A1 Pujol-Borrell, Ricardo
A1 Soler-Palacín, Pere
A1 Colobran, Roger
K1 TruSight one sequencing panel
K1 clinical exome sequencing
K1 genetic variants
K1 mutations
K1 next generation sequencing
K1 primary immunodeficiencies
AB Primary immunodeficiencies (PIDs) refer to a clinically, immunologically, and genetically heterogeneous group of over 350 disorders affecting development or function of the immune system. The increasing use of next-generation sequencing (NGS) technology has greatly facilitated identification of genetic defects in PID patients in daily clinical practice. Several NGS approaches are available, from the unbiased whole exome sequencing (WES) to specific gene panels. Here, we report on a 3-year experience with clinical exome sequencing (CES) for genetic diagnosis of PIDs. We used the TruSight One sequencing panel, which includes 4,813 disease-associated genes, in 61 unrelated patients (pediatric and adults). The analysis was done in 2 steps: first, we focused on a virtual PID panel and then, we expanded the analysis to the remaining genes. A molecular diagnosis was achieved in 19 (31%) patients: 12 (20%) with mutations in genes included in the virtual PID panel and 7 (11%) with mutations in other genes. These latter cases provided interesting and somewhat unexpected findings that expand the clinical and genetic spectra of PID-related disorders, and are useful to consider in the differential diagnosis. We also discuss 5 patients (8%) with incomplete genotypes or variants of uncertain significance. Finally, we address the limitations of CES exemplified by 7 patients (11%) with negative results on CES who were later diagnosed by other approaches (more specific PID panels, WES, and comparative genomic hybridization array). In summary, the genetic diagnosis rate using CES was 31% (including a description of 12 novel mutations), which rose to 42% after including diagnoses achieved by later use of other techniques. The description of patients with mutations in genes not included in the PID classification illustrates the heterogeneity and complexity of PID-related disorders.
YR 2019
FD 2019-10-01
LK http://hdl.handle.net/10668/14625
UL http://hdl.handle.net/10668/14625
LA en
DS RISalud
RD Apr 7, 2025