TY - JOUR
T1 - Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses
AU - Demidov, German
AU - Yaldiz, Burcu
AU - Garcia-Pelaez, José
AU - Solve-RD Consortium
AU - de Boer, Elke
AU - Schuermans, Nika
AU - Van de Vondel, Liedewei
AU - Paramonov, Ida
AU - Johansson, Lennart F.
AU - Musacchia, Francesco
AU - Benetti, Elisa
AU - Bullich, Gemma
AU - Sablauskas, Karolis
AU - Beltran, Sergi
AU - Gilissen, Christian
AU - Hoischen, Alexander
AU - Ossowski, Stephan
AU - de Voer, Richarda
AU - Lohmann, Katja
AU - Oliveira, Carla
AU - Topf, Ana
AU - Vissers, Lisenka E.L.M.
AU - Zguro, Kristina
AU - Zara, Federico
AU - Zaganas, Ioannis
AU - Yépez, Vicente A.
AU - Wirth, Brunhilde
AU - Webb, David
AU - Verdin, Hannah
AU - Van Nieuwenhove, Erika
AU - van Montfrans, Joris
AU - van Heurck, Roxane
AU - van der Veken, Lars
AU - Valle, Laura
AU - Uva, Paolo
AU - Udd, Bjarne
AU - Trimouille, Aurelien
AU - Thompson, Rachel
AU - Tartaglia, Marco
AU - Sznajer, Yves
AU - Striano, Pasquale
AU - Steinke-Lange, Verena
AU - Spilioti, Martha
AU - Scudieri, Paolo
AU - Schröck, Evelin
AU - Poppe, Bruce
AU - Leavis, Helen
AU - Köhler, Sebastian
AU - Kleefstra, Tjitske
AU - Heutink, Peter
AU - Riess, Olaf
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024/10/26
Y1 - 2024/10/26
N2 - We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs.
AB - We report the results of a comprehensive copy number variant (CNV) reanalysis of 9171 exome sequencing datasets from 5757 families affected by a rare disease (RD). The data reanalysed was extremely heterogeneous, having been generated using 28 different enrichment kits by 42 different research groups across Europe partnering in the Solve-RD project. Each research group had previously undertaken their own analysis of the data but failed to identify disease-causing variants. We applied three CNV calling algorithms to maximise sensitivity, and rare CNVs overlapping genes of interest, provided by four partner European Reference Networks, were taken forward for interpretation by clinical experts. This reanalysis has resulted in a molecular diagnosis being provided to 51 families in this sample, with ClinCNV performing the best of the three algorithms. We also identified partially explanatory pathogenic CNVs in a further 34 individuals. This work illustrates the value of reanalysing ES cold cases for CNVs.
UR - https://www.scopus.com/pages/publications/85207830154
U2 - 10.1038/s41525-024-00436-6
DO - 10.1038/s41525-024-00436-6
M3 - Article
C2 - 39461972
AN - SCOPUS:85207830154
SN - 2056-7944
VL - 9
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 49
ER -