Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia.

TitleWhole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia.
Publication TypeJournal Article
Year of Publication2014
AuthorsPehlivan, D, Karaca, E, Aydin, H, Beck, CR, Gambin, T, Muzny, DM, B Geckinli, B, Karaman, A, Jhangiani, SN, Gibbs, RA, Lupski, JR
Corporate AuthorsCenters for Mendelian Genomics
JournalEur J Hum Genet
Date Published2014 Sep
KeywordsAbnormalities, Multiple, Calcium Channels, Exome, Humans, Infant, Intellectual Disability, Male, Membrane Proteins, Mutation, Protein Isoforms

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.

Alternate JournalEur J Hum Genet
PubMed ID24424126
PubMed Central IDPMC4135405
Grant ListU54 HD083092 / HD / NICHD NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
U54HG006542 / HG / NHGRI NIH HHS / United States

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