OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Frontiers in Cell and Developmental Biology Année : 2022

OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants

Nolwenn Jean-Marçais
  • Fonction : Auteur
Alexandra Afenjar
  • Fonction : Auteur
  • PersonId : 902592
Arthur Sorlin
  • Fonction : Auteur
Sébastien Moutton
  • Fonction : Auteur

Résumé

Purpose: Patients with rare or ultra-rare genetic diseases, which affect 350 million people worldwide, may experience a diagnostic odyssey. High-throughput sequencing leads to an etiological diagnosis in up to 50% of individuals with heterogeneous neurodevelopmental or malformation disorders. There is a growing interest in additional omics technologies in translational research settings to examine the remaining unsolved cases. Methods: We gathered 30 individuals with malformation syndromes and/or severe neurodevelopmental disorders with negative trio exome sequencing and array comparative genomic hybridization results through a multicenter project. We applied short-read genome sequencing, total RNA sequencing, and DNA methylation analysis, in that order, as complementary translational research tools for a molecular diagnosis. Results: The cohort was mainly composed of pediatric individuals with a median age of 13.7 years (4 years and 6 months to 35 years and 1 month). Genome sequencing alone identified at least one variant with a high level of evidence of pathogenicity in 8/30 individuals (26.7%) and at least a candidate disease-causing variant in 7/30 other individuals (23.3%). RNA-seq data in 23 individuals allowed two additional individuals (8.7%) to be diagnosed, confirming the implication of two pathogenic variants (8.7%), and excluding one candidate variant (4.3%). Finally, DNA methylation analysis confirmed one diagnosis identified by genome sequencing (Kabuki syndrome) and identified an episignature compatible with a BAFopathy in a patient with a clinical diagnosis of Coffin-Siris with negative genome and RNA-seq results in blood. Conclusion: Overall, our integrated genome, transcriptome, and DNA methylation analysis solved 10/30 (33.3%) cases and identified a strong candidate gene in 4/30 (13.3%) of the patients with rare neurodevelopmental disorders and negative exome sequencing results.
Fichier principal
Vignette du fichier
Colin-2022-OMIXCARE- OMICS technologies.pdf (2.91 Mo) Télécharger le fichier
Data Sheet 1.pdf (560.4 Ko) Télécharger le fichier
Image 1.TIF (2.26 Mo) Télécharger le fichier
Image 2.TIFF (1.18 Mo) Télécharger le fichier
Image 3.TIFF (2.3 Mo) Télécharger le fichier
Table 1.XLSX (98.88 Ko) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03886419 , version 1 (06-12-2022)

Licence

Paternité

Identifiants

Citer

Estelle Colin, Yannis Duffourd, Emilie Tisserant, Raissa Relator, Ange-Line Bruel, et al.. OMIXCARE: OMICS technologies solved about 33% of the patients with heterogeneous rare neuro-developmental disorders and negative exome sequencing results and identified 13% additional candidate variants. Frontiers in Cell and Developmental Biology, 2022, 10, pp.1021785. ⟨10.3389/fcell.2022.1021785⟩. ⟨hal-03886419⟩
82 Consultations
56 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More