Universität zu Köln

Fazeli, Walid, Herkenrath, Peter, Stiller, Barbara, Neugebauer, Antje, Fricke, Julia, Lang-Roth, Ruth, Nuernberg, Gudrun, Thoenes, Michaela, Becker, Jutta, Altmueller, Janine, Volk, Alexander E., Kubisch, Christian ORCID: 0000-0003-4220-0978 and Heller, Raoul (2017). A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction. Hum. Mol. Genet., 26 (20). S. 4055 - 4067. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

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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 Mobius 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fazeli, Walid UNSPECIFIED UNSPECIFIED UNSPECIFIED Herkenrath, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Stiller, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Neugebauer, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Fricke, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lang-Roth, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Thoenes, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jutta UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Volk, Alexander E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubisch, Christian UNSPECIFIED orcid.org/0000-0003-4220-0978 UNSPECIFIED Heller, Raoul UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-214246
DOI:	10.1093/hmg/ddx296
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	26
Number:	20
Page Range:	S. 4055 - 4067
Date:	2017
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-TUBULIN ISOTYPES; CRANIAL DYSINNERVATION DISORDERS; EXTRAOCULAR-MUSCLES TYPE-2; CORTICAL DEVELOPMENT; NEURONAL MIGRATION; LINKAGE ANALYSIS; MOEBIUS SYNDROME; FIBROSIS; MALFORMATIONS; POLYMICROGYRIA Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21424