title: Novel IFT122 mutations in three Argentinian patients with cranioectodermal dysplasia: Expanding the mutational spectrum.
abstract: Cranioectodermal dysplasia (CED), also known as Sensenbrenner syndrome, is an autosomal recessive ciliary chondrodysplasia characterized by a recognizable craniofacial gestalt, skeletal abnormalities, and ectodermal features. To date, four genes have been shown to underlie the syndrome, namely, IFT122 (WDR10), WDR35 (IFT121), IFT43 (C14orf179), and WDR19 (IFT144). Clinical characterization of a larger cohort of patients with CED has been undertaken previously. Nevertheless, there are too few molecularly confirmed patients reported in the literature to determine precise genotype-phenotype correlations. To date, biallelic IFT122 mutations have been described in only five families. We therefore studied three unrelated Argentinian patients with typical features of CED using a 4813 next-generation sequencing (NGS) gene panel, which we call the "Mendeliome." The three patients had different, novel, compound heterozygous mutations in IFT122. Consequently, we compared these three patients to those previously described with IFT122 mutations. Thus, our report serves to add 6 novel mutations to the IFT122 mutation spectrum and to contribute to the IFT122-related clinical characterization.
authors.affiliation: Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.|Institute of Human Genetics, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Shahida
authors.initials: S
authors.lastname: Moosa
authors.affiliation: Department of Medical Genetics, Garrahan Pediatrics Hospital, Buenos Aires, Argentina.
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Obregon
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany.|Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Altmüller
authors.affiliation: Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.affiliation: Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.|Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.affiliation: Department of Growth and Development, Garrahan Pediatrics Hospital, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Fano
authors.affiliation: Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.|Institute of Human Genetics, University of Cologne, Cologne, Germany.|Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wollnik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001118:Argentina; D001842:Bone and Bones / Q000002:abnormalities* / Q000503:physiopathology; D002648:Child; D003398:Craniosynostoses / Q000235:genetics* / Q000503:physiopathology; D003598:Cytoskeletal Proteins; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011506:Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C422843:IFT122 protein, human; D011506:Proteins
keywords: CED-1; IFT122; Sensenbrenner syndrome; cranioectodermal dysplasia