title: Compound heterozygous mutations in the IFT140 gene cause Opitz trigonocephaly C syndrome in a patient with typical features of a ciliopathy.
abstract: 〈 We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also had manifestations of ciliopathy, including short ribs (non-asphyxiating), trident acetabular roofs, postaxial polydactyly cone-shaped epiphyses, and dysplasia of the renal, hepatic and pancreatic tissues. To investigate the molecular cause, we used an exome sequencing strategy followed by Sanger sequencing. Two rare variants, both predicted to result in loss of functional protein, were identified in the IFT140 gene; a substitution at the splice donor site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first coding exon (c.-11_6del). The variants were confirmed as being biallelic using Sanger sequencing, showing that the splice variant was inherited from the propositus mother and the deletion from the father. To date, Mainzer-Saldino syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been identified as ciliopathies caused by IFT140 mutations. We provide the first description of an OTCS phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.
authors.affiliation: Center for Registry and Research on Congenital Anomalies (CRIAC), Division of Pediatrics, Service of Genetics and Cytogenetic Unit, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Peña-Padilla
authors.affiliation: The Centre for Applied Genomics, Genetics and Genome Biology, Toronto, Canada.|Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada.
authors.forename: C R
authors.initials: CR
authors.lastname: Marshall
authors.affiliation: The Centre for Applied Genomics, Genetics and Genome Biology, Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Walker
authors.affiliation: The Centre for Applied Genomics, Genetics and Genome Biology, Toronto, Canada.|Department of Molecular Genetics and the McLaughlin Centre, University of Toronto, Toronto, Canada.
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: Service of Pathology, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Tavares-Macías
authors.affiliation: Service of Pathology, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Razo-Jiménez
authors.affiliation: Center for Registry and Research on Congenital Anomalies (CRIAC), Division of Pediatrics, Service of Genetics and Cytogenetic Unit, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.|"Dr. Enrique Corona-Rivera" Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: L
authors.initials: L
authors.lastname: Bobadilla-Morales
authors.affiliation: Center for Registry and Research on Congenital Anomalies (CRIAC), Division of Pediatrics, Service of Genetics and Cytogenetic Unit, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Acosta-Fernández
authors.affiliation: Center for Registry and Research on Congenital Anomalies (CRIAC), Division of Pediatrics, Service of Genetics and Cytogenetic Unit, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.|"Dr. Enrique Corona-Rivera" Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Corona-Rivera
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Mendoza-Londono
authors.affiliation: Center for Registry and Research on Congenital Anomalies (CRIAC), Division of Pediatrics, Service of Genetics and Cytogenetic Unit, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Guadalajara, Mexico.|"Dr. Enrique Corona-Rivera" Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: J R
authors.initials: JR
authors.lastname: Corona-Rivera
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D000072661:Ciliopathies / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C000603049:IFT140 protein, human; D022821:RNA Splice Sites
keywords: C-syndrome; IFT140; craniosynostosis; renal-hepatic-pancreatic dysplasia; retinal dystrophy; trigonocephaly