title: A homozygous nonsense variant in IFT52 is associated with a human skeletal ciliopathy.
abstract: Intraflagellar transport (IFT) is vital for the functioning of primary cilia. Defects in several components of IFT complexes cause a spectrum of ciliopathies with variable involvement of skeleton, brain, eyes, ectoderm and kidneys. We examined a child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. The clinical phenotype of the child shows significant overlap with cranioectodermal dysplasia type I (Sensenbrenner syndrome). Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52 encoding an IFT-B core complex protein as the probable cause of her condition. This is the first report of a human disease associated with IFT52.
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: K M
authors.identifier: 0000-0002-0139-8239
authors.initials: KM
authors.lastname: Girisha
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: A
authors.initials: A
authors.lastname: Shukla
authors.affiliation: Department of Bioinformatics, Centogene AG, Rostock, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Trujillano
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: G S
authors.initials: GS
authors.lastname: Bhavani
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: M
authors.initials: M
authors.lastname: Hebbar
authors.affiliation: Department of Radiodiagnosis and Imaging, Kasturba Medical College, Manipal University, Manipal, India.
authors.forename: R
authors.initials: R
authors.lastname: Kadavigere
authors.affiliation: Department of Bioinformatics, Centogene AG, Rostock, Germany.|Albrecht-Kossel-Institute for Neuroregeneration, Medical University Rostock, Rostock, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Rolfs
mesh_terms: D001842:Bone and Bones / Q000002:abnormalities* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D002923:Cilia / Q000473:pathology; D000072661:Ciliopathies / Q000235:genetics* / Q000503:physiopathology; D003398:Craniosynostoses / Q000235:genetics* / Q000503:physiopathology; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; C000621073:IFT52 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; C412724:TRAF3IP1 protein, human
keywords: chondrodysplasia; ciliopathy; exome sequencing; intraflagellar transport; sensenbrenner syndrome; short rib thoracic dysplasia