---
_id: '1016'
abstract:
- lang: eng
text: The integrity and dynamic properties of the microtubule cytoskeleton are indispensable
for the development of the mammalian brain. Consequently, mutations in the genes
that encode the structural component (the α/β-tubulin heterodimer) can give rise
to severe, sporadic neurodevelopmental disorders. These are commonly referred
to as the tubulinopathies. Here we report the addition of recessive quadrupedalism,
also known as Uner Tan syndrome (UTS), to the growing list of diseases caused
by tubulin variants. Analysis of a consanguineous UTS family identified a biallelic
TUBB2B mutation, resulting in a p.R390Q amino acid substitution. In addition to
the identifying quadrupedal locomotion, all three patients showed severe cerebellar
hypoplasia. None, however, displayed the basal ganglia malformations typically
associated with TUBB2B mutations. Functional analysis of the R390Q substitution
revealed that it did not affect the ability of β-tubulin to fold or become assembled
into the α/β-heterodimer, nor did it influence the incorporation of mutant-containing
heterodimers into microtubule polymers. The 390Q mutation in S. cerevisiae TUB2
did not affect growth under basal conditions, but did result in increased sensitivity
to microtubule-depolymerizing drugs, indicative of a mild impact of this mutation
on microtubule function. The TUBB2B mutation described here represents an unusual
recessive mode of inheritance for missense-mediated tubulinopathies and reinforces
the sensitivity of the developing cerebellum to microtubule defects.
article_processing_charge: No
author:
- first_name: Martin
full_name: Breuss, Martin
last_name: Breuss
- first_name: Thai
full_name: Nguyen, Thai
last_name: Nguyen
- first_name: Anjana
full_name: Srivatsan, Anjana
last_name: Srivatsan
- first_name: Ines
full_name: Leca, Ines
last_name: Leca
- first_name: Guoling
full_name: Tian, Guoling
last_name: Tian
- first_name: Tanja
full_name: Fritz, Tanja
last_name: Fritz
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Damir
full_name: Musaev, Damir
last_name: Musaev
- first_name: Jennifer
full_name: Mcevoy Venneri, Jennifer
last_name: Mcevoy Venneri
- first_name: James
full_name: Kiely, James
last_name: Kiely
- first_name: Rasim
full_name: Rosti, Rasim
last_name: Rosti
- first_name: Eric
full_name: Scott, Eric
last_name: Scott
- first_name: Uner
full_name: Tan, Uner
last_name: Tan
- first_name: Richard
full_name: Kolodner, Richard
last_name: Kolodner
- first_name: Nicholas
full_name: Cowan, Nicholas
last_name: Cowan
- first_name: David
full_name: Keays, David
last_name: Keays
- first_name: Joseph
full_name: Gleeson, Joseph
last_name: Gleeson
citation:
ama: Breuss M, Nguyen T, Srivatsan A, et al. Uner Tan syndrome caused by a homozygous
TUBB2B mutation affecting microtubule stability. Human Molecular Genetics.
2017;26(2):258-269. doi:10.1093/hmg/ddw383
apa: Breuss, M., Nguyen, T., Srivatsan, A., Leca, I., Tian, G., Fritz, T., … Gleeson,
J. (2017). Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting
microtubule stability. Human Molecular Genetics. Oxford University Press.
https://doi.org/10.1093/hmg/ddw383
chicago: Breuss, Martin, Thai Nguyen, Anjana Srivatsan, Ines Leca, Guoling Tian,
Tanja Fritz, Andi H Hansen, et al. “Uner Tan Syndrome Caused by a Homozygous TUBB2B
Mutation Affecting Microtubule Stability.” Human Molecular Genetics. Oxford
University Press, 2017. https://doi.org/10.1093/hmg/ddw383.
ieee: M. Breuss et al., “Uner Tan syndrome caused by a homozygous TUBB2B
mutation affecting microtubule stability,” Human Molecular Genetics, vol.
26, no. 2. Oxford University Press, pp. 258–269, 2017.
ista: Breuss M, Nguyen T, Srivatsan A, Leca I, Tian G, Fritz T, Hansen AH, Musaev
D, Mcevoy Venneri J, Kiely J, Rosti R, Scott E, Tan U, Kolodner R, Cowan N, Keays
D, Gleeson J. 2017. Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting
microtubule stability. Human Molecular Genetics. 26(2), 258–269.
mla: Breuss, Martin, et al. “Uner Tan Syndrome Caused by a Homozygous TUBB2B Mutation
Affecting Microtubule Stability.” Human Molecular Genetics, vol. 26, no.
2, Oxford University Press, 2017, pp. 258–69, doi:10.1093/hmg/ddw383.
short: M. Breuss, T. Nguyen, A. Srivatsan, I. Leca, G. Tian, T. Fritz, A.H. Hansen,
D. Musaev, J. Mcevoy Venneri, J. Kiely, R. Rosti, E. Scott, U. Tan, R. Kolodner,
N. Cowan, D. Keays, J. Gleeson, Human Molecular Genetics 26 (2017) 258–269.
date_created: 2018-12-11T11:49:42Z
date_published: 2017-01-01T00:00:00Z
date_updated: 2023-09-22T09:42:42Z
day: '01'
department:
- _id: SiHi
doi: 10.1093/hmg/ddw383
external_id:
isi:
- '000397066400002'
intvolume: ' 26'
isi: 1
issue: '2'
language:
- iso: eng
month: '01'
oa_version: None
page: 258 - 269
publication: Human Molecular Genetics
publication_identifier:
issn:
- '09646906'
publication_status: published
publisher: Oxford University Press
publist_id: '6379'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule
stability
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 26
year: '2017'
...