5 years ago

A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction.

Thoenes, Stiller, Herkenrath, Nürnberg, Volk, Altmüller, Heller, Lang-Roth, Kubisch, Becker, Neugebauer, Fricke, Fazeli
Congenital cranial dysinnervation disorders (CCDDs) comprise a heterogeneous spectrum of diseases characterized by congenital, non-progressive impairment of eye, eyelid and/or facial movements including Möbius syndrome, Duane retraction syndrome, congenital ptosis, and congenital fibrosis of the extraocular muscles. Over the last 20 years, several CCDDs have been identified as neurodevelopmental disorders that are caused by mutations of genes involved in brain and cranial nerve development, e.g. KIF21A and TUBB3 that each plays a pivotal role for microtubule function. In a five-generation pedigree, we identified a heterozygous mutation of TUBB6, a gene encoding a class V tubulin which has not been linked to a human hereditary disease so far. The missense mutation (p.Phe394Ser) affects an amino acid residue highly conserved in evolution, and co-segregates with a phenotype characterized by congenital non-progressive bilateral facial palsy and congenital velopharyngeal dysfunction presenting with varying degrees of hypomimia, rhinophonia, impaired gag reflex and bilateral ptosis. Expression of the mutated protein in yeast led to an impaired viability compared to wildtype cells when exposed to the microtubule-poison benomyl. Our findings enlarge the spectrum of tubulinopathies and emphasize that mutations of TUBB6 should be considered in patients with congenital non-progressive facial palsy. Further studies are needed to verify whether this phenotype is indeed part of the CCDD spectrum.

Publisher URL: http://doi.org/10.1093/hmg/ddx296

DOI: 10.1093/hmg/ddx296

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.