Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/38762
Title: Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects.
Authors: Park, J. G.
Tischfield, M. A.
Nugent, A. A.
Cheng, L.
Di Gioia, S. A.
Chan, W. M.
Maconachie, Gail
Bosley, T. M.
Summers, C. G.
Hunter, D. G.
Robson, C. D.
Gottlob, Irene
Engle, E. C.
First Published: 12-May-2016
Publisher: Elsevier (Cell Press)
Citation: American Journal of Human Genetics, 2016, 98 (6), pp. 1220-1227
Abstract: Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.
DOI Link: 10.1016/j.ajhg.2016.03.023
ISSN: 0002-9297
eISSN: 1537-6605
Links: http://www.sciencedirect.com/science/article/pii/S0002929716300581
http://hdl.handle.net/2381/38762
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Creative Commons “Attribution Non-Commercial No Derivatives” licence CC BY-NC-ND, further details of which can be found via the following link: http://creativecommons.org/licenses/by-nc-nd/4.0/ Archived with reference to SHERPA/RoMEO and publisher website.
Description: The accession numbers for the variants identified in this study are ClinVar: SCV000265995, SCV000265996, SCV000265997, and SCV000265998.
Appears in Collections:Published Articles, Dept. of Neuroscience, Psychology and Behaviour

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