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

Item Type:	Article
Title:	A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction
Creators Name:	Fazeli, W. and Herkenrath, P. and Stiller, B. and Neugebauer, A. and Fricke, J. and Lang-Roth, R. and Nürnberg, G. and Thoenes, M. and Becker, J. and Altmüller, J. and Volk, A.E. and Kubisch, C. and Heller, R.
Abstract:	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.
Keywords:	Blepharoptosis, Dominant Genes, Facial Paralysis, Mutation, Oculomotor Muscles, Pedigree, Tubulin, Velopharyngeal Insufficiency
Source:	Human Molecular Genetics
ISSN:	0964-6906
Publisher:	Oxford University Press
Volume:	26
Number:	20
Page Range:	4055-4066
Date:	15 October 2017
Official Publication:	https://doi.org/10.1093/hmg/ddx296
PubMed:	View item in PubMed

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