title: Haploinsufficiency of CELF4 at 18q12.2 is associated with developmental and behavioral disorders, seizures, eye manifestations, and obesity.
abstract: Only 20 patients with deletions of 18q12.2 have been reported in the literature and the associated phenotype includes borderline intellectual disability, behavioral problems, seizures, obesity, and eye manifestations. Here, we report a male patient with a de novo translocation involving chromosomes 12 and 18, with borderline IQ, developmental and behavioral disorders, myopia, obesity, and febrile seizures in childhood. We characterized the rearrangement with Affymetrix SNP 6.0 Array analysis and next-generation mate pair sequencing and found truncation of CELF4 at 18q12.2. This second report of a patient with a neurodevelopmental phenotype and a translocation involving CELF4 supports that CELF4 is responsible for the phenotype associated with deletion of 18q12.2. Our study illustrates the utility of high-resolution genome-wide techniques in identifying neurodevelopmental and neurobehavioral genes, and it adds to the growing evidence, including a transgenic mouse model, that CELF4 is important for human brain development.
authors.affiliation: Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark. halgren@sund.ku.dk
authors.forename: Christina
authors.initials: C
authors.lastname: Halgren
authors.forename: Iben
authors.initials: I
authors.lastname: Bache
authors.forename: Mads
authors.initials: M
authors.lastname: Bak
authors.forename: Mikkel Wanting
authors.initials: MW
authors.lastname: Myatt
authors.forename: Claire Marie
authors.initials: CM
authors.lastname: Anderson
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
mesh_terms: D000328:Adult; D000067878:CELF Proteins; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D006801:Humans; D008297:Male; D009216:Myopia / Q000175:diagnosis / Q000235:genetics*; D009765:Obesity / Q000175:diagnosis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D012640:Seizures / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: D000067878:CELF Proteins; C422243:CELF4 protein, human; D016601:RNA-Binding Proteins