title: Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia.
abstract: Whole-exome sequencing (WES) is a type of disruptive technology that has tremendous influence on human and clinical genetics research. An efficient and cost-effective method, WES is now widely used as a diagnostic tool for identifying the molecular basis of genetic syndromes that are often challenging to diagnose. Here we report a patient with a clinical diagnosis of cerebro-facio-thoracic dysplasia (CFTD; MIM#213980) in whom we identified a homozygous splice-site mutation in the transmembrane and coiled-coil domains 1 (TMCO1) gene using WES. TMCO1 mutations cause craniofacial dysmorphism, skeletal anomalies characterized by multiple malformations of the vertebrae and ribs, and intellectual disability (MIM#614132). A retrospective review revealed that clinical manifestations of both syndromes are very similar and overlap remarkably. We propose that mutations of TMCO1 are not only responsible for craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome but also for CFTD.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Davut
authors.initials: D
authors.lastname: Pehlivan
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ender
authors.initials: E
authors.lastname: Karaca
authors.affiliation: Center of Genetics Diagnosis, Zeynep Kamil Maternity and Children's Training and Research Hospital, Istanbul, Turkey.
authors.forename: Hatip
authors.initials: H
authors.lastname: Aydin
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Christine R
authors.initials: CR
authors.lastname: Beck
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Center of Genetics Diagnosis, Zeynep Kamil Maternity and Children's Training and Research Hospital, Istanbul, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Bilge Geckinli
authors.affiliation: Center of Genetics Diagnosis, Zeynep Kamil Maternity and Children's Training and Research Hospital, Istanbul, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Karaman
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Shalini N
authors.initials: SN
authors.lastname: Jhangiani
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA [3] Texas Children's Hospital, Houston, TX, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D015220:Calcium Channels; D059472:Exome; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D020033:Protein Isoforms; C575495:TMCO1 protein, human