{"database": "metadata", "table": "run_metadata", "rows": [[74909, "SRR24130496", "SRX19929337", "SRS17279404", "SRP431990", "PRJNA954363", "Biallelic variants in CSPG4 cause a novel neurodevelopmental disorder with intellectual disability  global developmental delay and facial anomalies", "GSE229401", "Transcriptome Analysis", "We aimed to define a novel autosomal recessive neurodevelopmental disorder  characterize its clinical features  and identify the underlying genetic cause for this condition. Clinical and genetic data from affected individuals with neurological disorders were matched across families from five global sites. Here  we report five recessive CSPG4 NM 001897 missense variants [three homozygous: c.A1370G p.Asp457Gly  c.2627G>A p.Arg876His and c.3247C>A p.Gln1083Lys  and two compound heterozygous: c.A1370G and c.5156A>G p.Asp457Gly and p.Gln1719Arg and c.658A>G and c.1220 1221delinsTG p.Thr220Ala and p.Pro407Leu] by next generation sequencing of five unrelated families with seven affected subjects. All subjects share a novel neurodevelopmental syndrome characterized by severe intellectual disability  global developmental delay  delayed ability to walk  speech and language delay  distinctive facial features  along with varying degrees of neurological impairment  including hypotonia  cerebellar hypoplasia  and/or seizures. All CSPG4 variants were predicted to be damaging using in silico tools  and three dimensional molecular modeling suggested significant alterations in protein stability  compromising inter  and intra molecular interactions. The impact on neurological and craniofacial development was analyzed in CRISPR/Cas9 mediated zebrafish models. CSPG4 variants affected notochord development  neuronal function  and cerebellar structure along with a disorganized head scaffold with anomalous skeletal and cartilage components. Two individuals metabolomics and crispant transcriptomics revealed significant perturbation of metabolites  extracellular matrix ECM regulating pathways  and genes previously described to cause mental retardation  dwarfism  and facial anomalies in humans. Our study links novel  rare  damaging variants of the ECM gene CSPG4 to a novel recessive Mendelian neurodevelopmental disorder in humans and supports the role of CSPG4 in early development. Overall design: Zebrafish CSPG4 model RNA sequencing.  We used RNA sequencing of dissected heads from n=20 animals of each group  in 3 independent replicates.", null, null, null, "CSPG4 Control 2", "GSM7162841", null, "source name:pooled heads|tissue:pooled heads|treatment:wildtype|geo loc name:missing|collection date:missing", "CSPG4 Control 2", "Reads were mapped to the Danio rerio GRCz11 Genome Reference Consortium Zebrafish Build 11  INSDC Assembly GCA 000002035.4  May 2017using STAR 2.6.1d aligner HTSeq count v0.9.1 was used to generate the raw counts. We used Limma voom to normalize the raw counts. Differentially expressed genes DEGs between zebrafish CSPG4 model and WT controls were identified as described previously Unlu  Qi et al. 2020. Data in fastq format were mapped to the zebrafish Danio rerio genome assembly GRCz11 danRer11 [https://www.ncbi.nlm.nih.gov/grc/zebrafish] using STAR aligner v2.6.1d [https://github.com/alexdobin/STAR]. Reads were summarized using Counts v2.0.0 [http://subread.sourceforge.net/]. Differential expression analysis was performed using the limma package [https://bioconductor.org/packages/release/bioc/html/limma.html]  and gene set enrichment analysis GSEA was performed using Cluster Profiler package [https://bioconductor.org/packages/release/bioc/html/clusterProfiler.html]. Assembly: GRCz11 Supplementary files format and content: Gene list Supplemental Table 2.xls  SPG4 ZF CRISPANTS LEX8 Rawcounts.tsv", "pooled heads", null, "mRNA libraries were prepared using Lexogen QuantSeq 3\u2019 mRNA Seq Library Prep Kit according to manufacturer's protocols. three prime mRNA Seq", null, "tissue:pooled heads|treatment:wildtype", "GSM7162841", "GSM7162841: CSPG4 Control 2; Danio rerio; RNA Seq", "GSM7162841 r1", "GSM7162841", "1", "mRNA libraries were prepared using Lexogen QuantSeq three prime mRNA Seq Library Prep Kit according to manufacturer's protocols. three prime mRNA Seq", null, "RNA-Seq", "TRANSCRIPTOMIC", "cDNA", "SINGLE", "ILLUMINA", "NextSeq 500", null, "SRP431990", null, null, "CSP_CR_C2_R1.fastq.gz", "fastq", 881288324.0, 11595899.0, "GSM7162841 r1", "0:76 1:0", "A:262460545;C:180443987;G:195444043;T:242934708;N:5041", 76, 0, null, null, 262460545, 180443987, 195444043, 242934708, 5041, "SRX19929337", "SRS17279404", "SRA1622718", "Sidra Medicine", "Sidra Medicine", 1, 0.71545, null, 0.09599, null, 0.78182, null, 0.46812, null, 76, null, "B", null, "usable mapping rate", "illumina", "nextseq", "3prime", "cdna_unspecified", "lexogen", "bulk", "unknown", "unknown", null, "Qatar", "2023-04-11", "Undetermined", "Undetermined", "Head", "Nervous System"]], "columns": ["rowid", "run.accession", "experiment.accession", "sample.accession", "study.accession", "bioproject", "study.title", "study.alias", "study.type", "study.abstract", "study.attributes", "study.PMIDs", "sample.description", "sample.title", "sample.alias", "sample.centername", "sample.attributes", "GEOsample.title", "GEOsample.dataprocessing", "GEOsample.source", "GEOsample.treatmentprotocol", "GEOsample.extractprotocol", "GEOsample.growthprotocol", "GEOsample.characteristics", "GEOsample.accession", "experiment.title", "experiment.alias", "experiment.library_name", "experiment.design_description", "experiment.library_construction_protocol", "experiment.attributes", "experiment.library_strategy", "experiment.library_source", "experiment.library_selection", "experiment.library_layout", "experiment.platform", "experiment.instrument_model", "experiment.spot_descriptor", "experiment.study_ref", "run.title", "run.attributes", "run.filename", "run.semantic_name", "run.total_bases", "run.total_spots", "run.alias", "run.read_lengths", "run.base_counts", "run.r1_length", "run.r2_length", "run.r3_length", "run.r4_length", "run.Acount", "run.Ccount", "run.Gcount", "run.Tcount", "run.Ncount", "run.experiment", "run.pool_member", "submission.accession", "submission.srasource", "submission.bioprojectsource", "seqdetective.n_mates", "seqdetective.mapping_rate.mate1", "seqdetective.mapping_rate.mate2", "seqdetective.nofeature_rate.mate1", "seqdetective.nofeature_rate.mate2", "seqdetective.sparsity.mate1", "seqdetective.sparsity.mate2", "seqdetective.pos_strand_rate.mate1", "seqdetective.pos_strand_rate.mate2", "seqdetective.readlen.mate1", "seqdetective.readlen.mate2", "seqdetective.judgement.mate1", "seqdetective.judgement.mate2", "seqdetective.judgement.reason", "platform_family", "instrument_generation", "read_bias", "selection_class", "prep_kit", "sc_or_bulk", "tech_class", "technology", "tech_variant", "submission.bioprojectsource.country", "earliest_date", "devstage_curation", "devstage_curation_coarse", "tissue_curation", "tissue_curation_coarse"], "primary_keys": ["rowid"], "primary_key_values": ["74909"], "units": {}, "query_ms": 14.815659989835694}