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

التفاصيل البيبلوغرافية
العنوان:	A TUBB6 mutation is associated with autosomal dominant non-progressive congenital facial palsy, bilateral ptosis and velopharyngeal dysfunction
المؤلفون:	Michaela Thoenes, Peter Herkenrath, Jutta Becker, Gudrun Nürnberg, Ruth Lang-Roth, Walid Fazeli, Julia Fricke, Barbara Stiller, Antje Neugebauer, Janine Altmüller, Raoul Heller, Alexander E Volk, Christian Kubisch
المصدر:	Human molecular genetics 26(20), 4055-4066 (2017). doi:10.1093/hmg/ddx296
سنة النشر:	2017
مصطلحات موضوعية:	0301 basic medicine, Male, Pathology, Möbius syndrome, Velopharyngeal Insufficiency, Hypomimia, Facial Nerve Diseases, 0302 clinical medicine, Tubulin, Congenital fibrosis of the extraocular muscles, Missense mutation, Blepharoptosis, complications [Blepharoptosis], Genetics (clinical), Genes, Dominant, Bilateral facial palsy, pathology [Blepharoptosis], General Medicine, Middle Aged, pathology [Facial Paralysis], Facial paralysis, Pedigree, pathology [Velopharyngeal Insufficiency], Child, Preschool, genetics [Velopharyngeal Insufficiency], Female, medicine.symptom, medicine.medical_specialty, congenital [Velopharyngeal Insufficiency], Facial Paralysis, genetics [Tubulin], Biology, 03 medical and health sciences, genetics [Blepharoptosis], ddc:570, genetics [Facial Paralysis], Genetics, medicine, Humans, Molecular Biology, TUBB6 protein, human, pathology [Oculomotor Muscles], Bell Palsy, medicine.disease, 030104 developmental biology, Oculomotor Muscles, Mutation, congenital [Facial Paralysis], 030217 neurology & neurosurgery
الوصف:	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.
تدمد:	1460-2083
الوصول الحر:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53f54eb9bb550dfb23fbd85d6e149d11Test https://pubmed.ncbi.nlm.nih.gov/29016863Test
حقوق:	OPEN
رقم الانضمام:	edsair.doi.dedup.....53f54eb9bb550dfb23fbd85d6e149d11
قاعدة البيانات:	OpenAIRE

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