eprintid: 1546386
rev_number: 62
eprint_status: archive
userid: 608
dir: disk0/01/54/63/86
datestamp: 2017-04-03 13:34:25
lastmod: 2021-09-19 23:59:22
status_changed: 2017-04-03 13:34:25
type: article
metadata_visibility: show
creators_name: Xu, M
creators_name: Xie, YA
creators_name: Abouzeid, H
creators_name: Gordon, CT
creators_name: Fiorentino, A
creators_name: Sun, Z
creators_name: Lehman, A
creators_name: Osman, IS
creators_name: Dharmat, R
creators_name: Riveiro-Alvarez, R
creators_name: Bapst-Wicht, L
creators_name: Babino, D
creators_name: Arno, G
creators_name: Busetto, V
creators_name: Zhao, L
creators_name: Li, H
creators_name: Lopez-Martinez, MA
creators_name: Azevedo, LF
creators_name: Hubert, L
creators_name: Pontikos, N
creators_name: Eblimit, A
creators_name: Lorda-Sanchez, I
creators_name: Kheir, V
creators_name: Plagnol, V
creators_name: Oufadem, M
creators_name: Soens, ZT
creators_name: Yang, L
creators_name: Bole-Feysot, C
creators_name: Pfundt, R
creators_name: Allaman-Pillet, N
creators_name: Nitschké, P
creators_name: Cheetham, ME
creators_name: Lyonnet, S
creators_name: Agrawal, SA
creators_name: Li, H
creators_name: Pinton, G
creators_name: Michaelides, M
creators_name: Besmond, C
creators_name: Li, Y
creators_name: Yuan, Z
creators_name: von Lintig, J
creators_name: Webster, AR
creators_name: Le Hir, H
creators_name: Stoilov, P
creators_name: UK Inherited Retinal Dystrophy Consortium, .
creators_name: Amiel, J
creators_name: Hardcastle, AJ
creators_name: Ayuso, C
creators_name: Sui, R
creators_name: Chen, R
creators_name: Allikmets, R
creators_name: Schorderet, DF
title: Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D08
divisions: C08
divisions: D09
divisions: F99
keywords: CRISPR-Cas9, CWC27, brachydachtyly, craniofacial defects, neurological defects, retinal degeneration, short stature, spliceosome, syndrome
note: Copyright © 2017 American Society of Human Genetics. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
abstract: Pre-mRNA splicing factors play a fundamental role in regulating transcript diversity both temporally and spatially. Genetic defects in several spliceosome components have been linked to a set of non-overlapping spliceosomopathy phenotypes in humans, among which skeletal developmental defects and non-syndromic retinitis pigmentosa (RP) are frequent findings. Here we report that defects in spliceosome-associated protein CWC27 are associated with a spectrum of disease phenotypes ranging from isolated RP to severe syndromic forms. By whole-exome sequencing, recessive protein-truncating mutations in CWC27 were found in seven unrelated families that show a range of clinical phenotypes, including retinal degeneration, brachydactyly, craniofacial abnormalities, short stature, and neurological defects. Remarkably, variable expressivity of the human phenotype can be recapitulated in Cwc27 mutant mouse models, with significant embryonic lethality and severe phenotypes in the complete knockout mice while mice with a partial loss-of-function allele mimic the isolated retinal degeneration phenotype. Our study describes a retinal dystrophy-related phenotype spectrum as well as its genetic etiology and highlights the complexity of the spliceosomal gene network.
date: 2017-04-06
date_type: published
official_url: http://dx.doi.org/10.1016/j.ajhg.2017.02.008
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1262269
doi: 10.1016/j.ajhg.2017.02.008
pii: S0002-9297(17)30075-7
lyricists_name: Arno, Gavin
lyricists_name: Cheetham, Michael
lyricists_name: Fiorentino, Alessia
lyricists_name: Hardcastle, Alison
lyricists_name: Michaelides, Michel
lyricists_name: Plagnol, Vincent
lyricists_name: Pontikos, Nikolas
lyricists_name: Webster, Andrew
lyricists_id: GARNO32
lyricists_id: MECHE52
lyricists_id: AFIOR33
lyricists_id: AJHAR52
lyricists_id: MMICH14
lyricists_id: VYPLA47
lyricists_id: NPONT28
lyricists_id: ARWEB82
actors_name: Hardcastle, Alison
actors_id: AJHAR52
actors_role: owner
full_text_status: public
publication: American Journal of Human Genetics
volume: 100
number: 4
pagerange: 592-604
event_location: United States
issn: 1537-6605
citation:        Xu, M;    Xie, YA;    Abouzeid, H;    Gordon, CT;    Fiorentino, A;    Sun, Z;    Lehman, A;                                                                                                                                                                                     ... Schorderet, DF; + view all <#>        Xu, M;  Xie, YA;  Abouzeid, H;  Gordon, CT;  Fiorentino, A;  Sun, Z;  Lehman, A;  Osman, IS;  Dharmat, R;  Riveiro-Alvarez, R;  Bapst-Wicht, L;  Babino, D;  Arno, G;  Busetto, V;  Zhao, L;  Li, H;  Lopez-Martinez, MA;  Azevedo, LF;  Hubert, L;  Pontikos, N;  Eblimit, A;  Lorda-Sanchez, I;  Kheir, V;  Plagnol, V;  Oufadem, M;  Soens, ZT;  Yang, L;  Bole-Feysot, C;  Pfundt, R;  Allaman-Pillet, N;  Nitschké, P;  Cheetham, ME;  Lyonnet, S;  Agrawal, SA;  Li, H;  Pinton, G;  Michaelides, M;  Besmond, C;  Li, Y;  Yuan, Z;  von Lintig, J;  Webster, AR;  Le Hir, H;  Stoilov, P;  UK Inherited Retinal Dystrophy Consortium, .;  Amiel, J;  Hardcastle, AJ;  Ayuso, C;  Sui, R;  Chen, R;  Allikmets, R;  Schorderet, DF;   - view fewer <#>    (2017)    Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies.                   American Journal of Human Genetics , 100  (4)   pp. 592-604.    10.1016/j.ajhg.2017.02.008 <https://doi.org/10.1016/j.ajhg.2017.02.008>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/1/CWC27_AJHG_MX_020817_accepted.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/7/CWC27_figure1_AJHG.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/13/CWC27_figure2_AJHG.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/19/CWC27_figure3_AJHG.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/24/CWC27_figure4_AJHG.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/33/CWC27_figure5_AJHG.pdf
document_url: https://discovery.ucl.ac.uk/id/eprint/1546386/39/CWC27_figure6_AJHG.pdf