title: Intellectual disability and non-compaction cardiomyopathy with a de novo NONO mutation identified by exome sequencing.
abstract: Pathogenic variants in the NONO gene have been most recently implicated in X-linked intellectual disability syndrome. This observation has been supported by studies of NONO-deficient mice showing that NONO has an important role in regulating inhibitory synaptic activity. Thus far, the phenotypic spectrum of affected patients remains limited. We applied whole exome sequencing to members of a family in which the proband was presented with a complex phenotype consisting of developmental delay, dysmorphism, and non-compaction cardiomyopathy. Exome analysis identified a novel de novo splice-site variant c.1171+1G>T in exon 11 of NONO gene that is suspected to abolish the donor splicing site. Thus, we propose that the phenotypic spectrum of NONO-related disorder is much broader than described and that pathogenic variants in NONO cause a recognizable phenotype.
authors.affiliation: Medical Genetics Institute, Meir Medical Center, Kfar Saba, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Reinstein
authors.affiliation: Laboratory of Molecular Medicine, Rambam Health Care Campus, Haifa, Israel.|Genomic Research Department, Emedgene Technologies, Tel Aviv, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Tzur
authors.affiliation: Department of Pediatric Neurology and Epilepsy Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Rony
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Genomics Research Center, Gene by Gene, Houston, TX, USA.
authors.forename: Concetta
authors.initials: C
authors.lastname: Bormans
authors.affiliation: Genomics Research Center, Gene by Gene, Houston, TX, USA.
authors.forename: Doron M
authors.initials: DM
authors.lastname: Behar
mesh_terms: D000293:Adolescent; D000328:Adult; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics*; D004268:DNA-Binding Proteins; D059472:Exome; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D050810:Octamer Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins