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

Eur J Hum Genet. 2014 Sep;22(9):1145-8. doi: 10.1038/ejhg.2013.291. Epub 2014 Jan 15.


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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Calcium Channels
  • Exome
  • Humans
  • Infant
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Mutation
  • Protein Isoforms / genetics


  • Calcium Channels
  • Membrane Proteins
  • Protein Isoforms
  • TMCO1 protein, human

Supplementary concepts

  • Cerebrofaciothoracic Dysplasia