title: De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia.
abstract: We report an 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. Array comparative genomic hybridization analysis identified a de novo 4.5-Mb microdeletion on chromosome 14q24.2q24.3. The deleted region and phenotype partially overlap with previously reported patients. Here, we provide an overview of the literature on 14q24 microdeletions and further delineate the associated phenotype. We performed exome sequencing to examine other causes for the phenotype and queried genes present in the 14q24.2q24.3 microdeletion that are associated with recessive disease for variants in the non-deleted allele. The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. Although Sanger and exome sequencing did not identify variants in the second IFT43 allele or in other IFT complex A-protein-encoding genes, immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marijn F
authors.initials: MF
authors.lastname: Stokman
authors.affiliation: Department of Human Genetics, Radboud Insitute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Machteld M
authors.initials: MM
authors.lastname: Oud
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: van Binsbergen
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Gisela G
authors.initials: GG
authors.lastname: Slaats
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nayia
authors.initials: N
authors.lastname: Nicolaou
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kirsten Y
authors.initials: KY
authors.lastname: Renkema
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Isaac J
authors.initials: IJ
authors.lastname: Nijman
authors.affiliation: Department of Human Genetics, Radboud Insitute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Roepman
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Giles
authors.affiliation: Department of Human Genetics, Radboud Insitute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.|Department of Biochemistry, University of Western Ontario, London, Canada.
authors.forename: Heleen H
authors.initials: HH
authors.lastname: Arts
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nine V A M
authors.initials: NV
authors.lastname: Knoers
authors.affiliation: Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mieke M
authors.initials: MM
authors.lastname: van Haelst
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D055028:Comparative Genomic Hybridization; D059472:Exome; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D056726:Genetic Association Studies; D006330:Heart Defects, Congenital / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D009216:Myopia / Q000235:genetics*; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; C561297:IFT43 protein, human
keywords: 14q24 microdeletion; IFT43; cilia; congenital heart defect; intellectual disability; skeletal anomalies