Comprehensive reanalysis for CNVs in ES data from unsolved rare disease cases results in new diagnoses.
Journal
NPJ genomic medicine
ISSN: 2056-7944
Titre abrégé: NPJ Genom Med
Pays: England
ID NLM: 101685193
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
14
02
2024
accepted:
25
09
2024
medline:
27
10
2024
pubmed:
27
10
2024
entrez:
27
10
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39461972
doi: 10.1038/s41525-024-00436-6
pii: 10.1038/s41525-024-00436-6
doi:
Types de publication
Journal Article
Langues
eng
Pagination
49Investigateurs
Olaf Riess
(O)
Tobias B Haack
(TB)
Holm Graessner
(H)
Birte Zurek
(B)
Kornelia Ellwanger
(K)
Marc Sturm
(M)
Joohyun Park
(J)
Leon Schütz
(L)
Julia M Schulze-Hentrich
(JM)
Rebecca Schüle
(R)
Jishu Xu
(J)
Melanie Kellner
(M)
Baptist Resch
(B)
Ingrid Kolen
(I)
Matthis Synofzik
(M)
Carlo Wilke
(C)
Andreas Traschütz
(A)
Danique Beijer
(D)
Peter Heutink
(P)
Ludger Schöls
(L)
Holger Hengel
(H)
Holger Lerche
(H)
Christian Boßelmann
(C)
Josua Kegele
(J)
Robert Lauerer-Braun
(R)
Stephan Lauxmann
(S)
Han Brunner
(H)
Hans Scheffer
(H)
Nicoline Hoogerbrugge
(N)
Peter A C 't Hoen
(PAC)
Wouter Steyaert
(W)
Richarda de Voer
(R)
Erik-Jan Kamsteeg
(EJ)
Bart van de Warrenburg
(B)
Nienke van Os
(N)
Iris Te Paske
(IT)
Erik Janssen
(E)
Elke de Boer
(E)
Marloes Steehouwer
(M)
Kornelia Neveling
(K)
Bart van der Sanden
(B)
Lydia Sagath
(L)
Tjitske Kleefstra
(T)
Anthony J Brookes
(AJ)
Spencer Gibson
(S)
Umar Riaz
(U)
Greg Warren
(G)
Sai Anuhya Nalagandla
(SA)
Yunze Patrick Wang
(YP)
Deepthi Sukumaran
(D)
Sadegh Abadijou
(S)
Volker Straub
(V)
Chiara Marini Bettolo
(CM)
Jordi Diaz Manera
(JD)
Sophie Hambleton
(S)
Karin Engelhardt
(K)
Jill Clayton-Smith
(J)
Siddharth Banka
(S)
Elizabeth Alexander
(E)
Adam Jackson
(A)
Laurence Faivre
(L)
Christel Thauvin
(C)
Antonio Vitobello
(A)
Anne-Sophie Denommé-Pichon
(AS)
Yannis Duffourd
(Y)
Ange-Line Bruel
(AL)
Victor Couturier
(V)
Ivo Glynne Gut
(IG)
Davide Piscia
(D)
Leslie Matalonga
(L)
Anastasios Papakonstantinou
(A)
Alberto Corvo
(A)
Marcos Fernandez-Callejo
(M)
Carles Hernández
(C)
Daniel Picó
(D)
Anna Esteve Codina
(AE)
Marc Dabad
(M)
Marta Gut
(M)
Emanuele Raineri
(E)
Gulcin Gumus
(G)
Virginie Bros-Facer
(V)
Ana Rath
(A)
Marc Hanauer
(M)
David Lagorce
(D)
Oscar Hongnat
(O)
Maroua Chahdil
(M)
Caterina Lucano
(C)
Emeline Lebreton
(E)
Giovanni Stevanin
(G)
Alexandra Durr
(A)
Claire-Sophie Davoine
(CS)
Léna Guillot-Noel
(L)
Anna Heinzmann
(A)
Giulia Coarelli
(G)
Gisèle Bonne
(G)
Teresinha Evangelista
(T)
Valérie Allamand
(V)
Isabelle Nelson
(I)
Rabah Ben Yaou
(R)
Corinne Metay
(C)
Bruno Eymard
(B)
Enzo Cohen
(E)
Antonio Atalaia
(A)
Tanya Stojkovic
(T)
Milan Macek
(M)
Marek Turnovec
(M)
Dana Thomasová
(D)
Radka Pourová Kremliková
(RP)
Vera Franková
(V)
Markéta Havlovicová
(M)
Lukáš Ryba
(L)
Petra Lišková
(P)
Pavla Doležalová
(P)
Alice Krebsová
(A)
Helen Parkinson
(H)
Thomas Keane
(T)
Mallory Freeberg
(M)
Coline Thomas
(C)
Dylan Spalding
(D)
Peter Robinson
(P)
Daniel Danis
(D)
Glenn Robert
(G)
Alessia Costa
(A)
Mike Hanna
(M)
Henry Houlden
(H)
Mary Reilly
(M)
Jana Vandrovcova
(J)
Stephanie Efthymiou
(S)
Heba Morsy
(H)
Elisa Cali
(E)
Francesca Magrinelli
(F)
Sanjay M Sisodiya
(SM)
Ravishankara Bellampalli
(R)
Patrick Moloney
(P)
Jonathan Rohrer
(J)
Francesco Muntoni
(F)
Irina Zaharieva
(I)
Anna Sarkozy
(A)
Luke Perry
(L)
Veronica Pini
(V)
Juliane Müller
(J)
Vincent Timmerman
(V)
Jonathan Baets
(J)
Geert de Vries
(G)
Jonathan De Winter
(J)
Peter de Jonghe
(P)
Liedewei Van de Vondel
(L)
Willem De Ridder
(W)
Sarah Weckhuysen
(S)
Hannah Stamberger
(H)
Charissa Millevert
(C)
Noor Smal
(N)
Vincenzo Nigro
(V)
Manuela Morleo
(M)
Michele Pinelli
(M)
Sandro Banfi
(S)
Annalaura Torella
(A)
Roberta Zeuli
(R)
Mariateresa Zanobio
(M)
Giulio Piluso
(G)
Alessandra Ferlini
(A)
Rita Selvatici
(R)
Francesca Gualandi
(F)
Stefania Bigoni
(S)
Marcella Neri
(M)
Stefan Aretz
(S)
Isabel Spier
(I)
Anna Katharina Sommer
(AK)
Sophia Peters
(S)
Rita Barbosa-Matos
(R)
Celina São José
(CS)
Marta Ferreira
(M)
Irene Gullo
(I)
Susana Fernandes
(S)
Luzia Garrido
(L)
Pedro Ferreira
(P)
Fátima Carneiro
(F)
Morris A Swertz
(MA)
Joeri K van der Velde
(JK)
Gerben van der Vries
(G)
Pieter B Neerincx
(PB)
Dieuwke Roelofs-Prins
(D)
David Ruvolo
(D)
Marielle van Gijn
(M)
Kristin M Abbott
(KM)
Wilhemina S Kerstjens Frederikse
(WS)
Eveline Zonneveld-Huijssoon
(E)
Sebastian Köhler
(S)
Alison Metcalfe
(A)
Richard Moore
(R)
Alain Verloes
(A)
Séverine Drunat
(S)
Delphine Heron
(D)
Cyril Mignot
(C)
Boris Keren
(B)
Jean-Madeleine de Sainte Agathe
(JM)
Rami Abou Jamra
(RA)
Marc Abramowicz
(M)
Özge Aksel Kiliçarslan
(ÖA)
Nicholas Allen
(N)
Francisco Javier Alonso García de la Rosa
(F)
Simona Balestrini
(S)
Peter Balicza
(P)
Tobias Bartolomaeus
(T)
Ayşe Nazl Başak
(AN)
Laura Batlle Masó
(LB)
David Beeson
(D)
Valerie Benoit
(V)
Katherine Benson
(K)
Eva Bermejo Sánchez
(EB)
Emilia K Bijlsma
(EK)
Elke Bogaert
(E)
Mara Bourbouli
(M)
Kaan Boztug
(K)
Sylvain Brohée
(S)
Susan Byrne
(S)
Andrés Caballero Garcia de Oteyza
(AC)
Gabriel Capella
(G)
Evelina Carpancea
(E)
Gianpiero Cavalleri
(G)
Ana Cazurro-Gutiérrez
(A)
Patrick F Chinnery
(PF)
Maria-Roberta Cilio
(MR)
Andrea Ciolfi
(A)
Kristl Claeys
(K)
Roger Colobran
(R)
Isabell Cordts
(I)
Judith Cossins
(J)
Karin Dahan
(K)
Bruno Dallapiccola
(B)
Norman Delanty
(N)
Christel Depienne
(C)
Chantal Depondt
(C)
Bart Dermaut
(B)
Marcus Deschauer
(M)
Julie Desir
(J)
Anne Destrée
(A)
Minas Drakos
(M)
Sarah Duerinckx
(S)
Berta Estevez
(B)
Athanasios Evangeliou
(A)
Chiara Fallerini
(C)
Marco Ferilli
(M)
Simone Furini
(S)
Julien Gagneur
(J)
Hamidah Ghani
(H)
Marie Greally
(M)
Bodo Grimbacher
(B)
Renzo Guerrini
(R)
Peter Hackman
(P)
Matthias Haimel
(M)
Eva Hammar Bouveret
(EH)
Dimitri Hemelsoet
(D)
Rebecca Herzog
(R)
Mariette J V Hoffer
(MJV)
Elke Holinski-Feder
(E)
Rita Horvath
(R)
Manon Huibers
(M)
Michele Iacomino
(M)
Mridul Johari
(M)
Elisabeth Kapaki
(E)
Deniz Karadurmus
(D)
Mert Karakaya
(M)
Evgenia Kokosali
(E)
Christian Korff
(C)
Leon Krass
(L)
Didier Lacombe
(D)
Andreas Laner
(A)
Helen Leavis
(H)
Damien Lederer
(D)
Elsa Leitão
(E)
Hanns Lochmüller
(H)
Estrella López Martín
(EL)
Rebeka Luknárová
(R)
Alfons Macaya
(A)
Sivasankar Malaichamy
(S)
Anna Marcé-Grau
(A)
Beatriz Martínez Delgado
(BM)
Sandrine Mary
(S)
Frédéric Masclaux
(F)
Lambros Mathioudakis
(L)
Ales Maver
(A)
Patrick May
(P)
Isabelle Maystadt
(I)
Davide Mei
(D)
Christian Mertes
(C)
Colombine Meunier
(C)
Maria Judit Molnar
(MJ)
Olivier Monestier
(O)
Stéphanie Moortgat
(S)
Alexander Münchau
(A)
Francina Munell
(F)
Andrés Nascimento Osorio
(AN)
Daniel Natera de Benito
(DN)
Mary O Reghan
(MO)
Catarina Olimpio
(C)
Elena Parrini
(E)
Martje Pauly
(M)
Belén Pérez-Dueñas
(B)
Borut Peterlin
(B)
Konrad Platzer
(K)
Kiran Polavarapu
(K)
Bruce Poppe
(B)
Manuel Posada De la Paz
(MP)
Flavia Privitera
(F)
Francesca Clementina Radio
(FC)
Thiloka Ratnaike
(T)
Alessandra Renieri
(A)
Antonella Riva
(A)
Caroline Rooryck
(C)
Andreas Roos
(A)
Claudia A L Ruivenkamp
(CAL)
Andreas Rump
(A)
Gijs W E Santen
(GWE)
Marco Savarese
(M)
Marcello Scala
(M)
Katherine Schon
(K)
Evelin Schröck
(E)
Paolo Scudieri
(P)
Martha Spilioti
(M)
Verena Steinke-Lange
(V)
Pasquale Striano
(P)
Yves Sznajer
(Y)
Marco Tartaglia
(M)
Rachel Thompson
(R)
Aurelien Trimouille
(A)
Bjarne Udd
(B)
Paolo Uva
(P)
Laura Valle
(L)
Lars van der Veken
(L)
Roxane van Heurck
(R)
Joris van Montfrans
(J)
Erika Van Nieuwenhove
(E)
Hannah Verdin
(H)
David Webb
(D)
Brunhilde Wirth
(B)
Vicente A Yépez
(VA)
Ioannis Zaganas
(I)
Federico Zara
(F)
Kristina Zguro
(K)
Informations de copyright
© 2024. The Author(s).
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