biostudies-literatureUnknown10Colin E<b>Purpose:</b> 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. <b>Methods:</b> 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 tranFrontiers in cell and developmental biology1021785https://www.ebi.ac.uk/biostudies/studies/S-EPMC9650323biostudies-literatureOMIXCARE: 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.PMC9650323Chevarin MRelator RKeren BMcConkey HBourgeois VMignot CFaivre LDuffourd YBoland ADenomme-Pichon ASPoe CDelanne JCallier PTran Mau-Them FFaudet ATisserant ECharles PJean-Marcais NSadikovic BColin EBruel ALSafraou HVitobello AVincent MAfenjar AThauvin-Robinet CHeron DIsidor BHeide SPhilippe CDeleuze JFOlaso ROdent SKerkhof JHerenger YSorlin AMoutton SCouturier VfalseOMIXCARE: 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.<b>Purpose:</b> 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. <b>Methods:</b> 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 tran2022-01-01T00:00:00Z20222026-07-14T15:21:30.424Z2024-10-19T05:12:42.38ZS-EPMC96503233639383110.3389/fcell.2022.1021785