---
_id: '7877'
abstract:
- lang: eng
text: The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount
for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS).
Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that
impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this
interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable
fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation.
Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication
inNIPBL, engineered in two different cell lines,alternative translation initiation
yields a form of NIPBL missing N-terminal residues. This form cannot interactwith
MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals
that cohesin loading can occur independently of functional NIPBL/MAU2 complexes
and highlights a novel mechanism protectiveagainst out-of-frame mutations that
is potentially relevant for other genetic conditions.
article_number: '107647'
article_processing_charge: No
article_type: original
author:
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Farah
full_name: Diab, Farah
last_name: Diab
- first_name: Sara Ruiz
full_name: Gil, Sara Ruiz
last_name: Gil
- first_name: Eskeatnaf
full_name: Mulugeta, Eskeatnaf
last_name: Mulugeta
- first_name: Valentina
full_name: Casa, Valentina
last_name: Casa
- first_name: Riccardo
full_name: Berutti, Riccardo
last_name: Berutti
- first_name: Rutger W.W.
full_name: Brouwer, Rutger W.W.
last_name: Brouwer
- first_name: Valerie
full_name: Dupé, Valerie
last_name: Dupé
- first_name: Juliane
full_name: Eckhold, Juliane
last_name: Eckhold
- first_name: Elisabeth
full_name: Graf, Elisabeth
last_name: Graf
- first_name: Beatriz
full_name: Puisac, Beatriz
last_name: Puisac
- first_name: Feliciano
full_name: Ramos, Feliciano
last_name: Ramos
- first_name: Thomas
full_name: Schwarzmayr, Thomas
last_name: Schwarzmayr
- first_name: Macarena Moronta
full_name: Gines, Macarena Moronta
last_name: Gines
- first_name: Thomas
full_name: Van Staveren, Thomas
last_name: Van Staveren
- first_name: Wilfred F.J.
full_name: Van Ijcken, Wilfred F.J.
last_name: Van Ijcken
- first_name: Tim M.
full_name: Strom, Tim M.
last_name: Strom
- first_name: Juan
full_name: Pié, Juan
last_name: Pié
- first_name: Erwan
full_name: Watrin, Erwan
last_name: Watrin
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Kerstin S.
full_name: Wendt, Kerstin S.
last_name: Wendt
citation:
ama: Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization
of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports.
2020;31(7). doi:10.1016/j.celrep.2020.107647
apa: Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt,
K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin
loader subunits and cause Cornelia de Lange syndrome. Cell Reports. Elsevier.
https://doi.org/10.1016/j.celrep.2020.107647
chicago: Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina
Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair
the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange
Syndrome.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.107647.
ieee: I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization
of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell
Reports, vol. 31, no. 7. Elsevier, 2020.
ista: Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé
V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren
T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2
and NIPBL variants impair the heterodimerization of the cohesin loader subunits
and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647.
mla: Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization
of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell
Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647.
short: I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer,
V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines,
T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser,
K.S. Wendt, Cell Reports 31 (2020).
date_created: 2020-05-24T22:00:57Z
date_published: 2020-05-19T00:00:00Z
date_updated: 2023-08-21T06:27:47Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.celrep.2020.107647
external_id:
isi:
- '000535655200005'
file:
- access_level: open_access
checksum: 64d8f7467731ee5c166b10b939b8310b
content_type: application/pdf
creator: dernst
date_created: 2020-05-26T11:05:01Z
date_updated: 2020-07-14T12:48:04Z
file_id: '7892'
file_name: 2020_CellReports_Parenti.pdf
file_size: 4695682
relation: main_file
file_date_updated: 2020-07-14T12:48:04Z
has_accepted_license: '1'
intvolume: ' 31'
isi: 1
issue: '7'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '05'
oa: 1
oa_version: Published Version
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader
subunits and cause Cornelia de Lange syndrome
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 31
year: '2020'
...
---
_id: '7957'
abstract:
- lang: eng
text: "Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain
development and function and are characterized by wide genetic and clinical variability.
In this review, we discuss the multiple factors that influence the clinical presentation
of NDDs, with particular attention to gene vulnerability, mutational load, and
the two-hit model. Despite the complex architecture of\r\nmutational events associated
with NDDs, the various proteins involved appear to converge on common pathways,
such as synaptic plasticity/function, chromatin remodelers and the mammalian target
of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind
these pathways will hopefully lead to the identification of candidates that could
be targeted for treatment approaches."
acknowledgement: We wish to thank Jasmin Morandell for generously sharing Figure 2.
This work was supported by the European Research Council Starting Grant (grant 715508
) to G.N.
article_processing_charge: No
article_type: original
author:
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Luis E
full_name: Garcia Rabaneda, Luis E
id: 33D1B084-F248-11E8-B48F-1D18A9856A87
last_name: Garcia Rabaneda
- first_name: Hanna
full_name: Schön, Hanna
id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
last_name: Schön
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders:
From genetics to functional pathways. Trends in Neurosciences. 2020;43(8):608-621.
doi:10.1016/j.tins.2020.05.004'
apa: 'Parenti, I., Garcia Rabaneda, L. E., Schön, H., & Novarino, G. (2020).
Neurodevelopmental disorders: From genetics to functional pathways. Trends
in Neurosciences. Elsevier. https://doi.org/10.1016/j.tins.2020.05.004'
chicago: 'Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino.
“Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends
in Neurosciences. Elsevier, 2020. https://doi.org/10.1016/j.tins.2020.05.004.'
ieee: 'I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental
disorders: From genetics to functional pathways,” Trends in Neurosciences,
vol. 43, no. 8. Elsevier, pp. 608–621, 2020.'
ista: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. 2020. Neurodevelopmental
disorders: From genetics to functional pathways. Trends in Neurosciences. 43(8),
608–621.'
mla: 'Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional
Pathways.” Trends in Neurosciences, vol. 43, no. 8, Elsevier, 2020, pp.
608–21, doi:10.1016/j.tins.2020.05.004.'
short: I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences
43 (2020) 608–621.
date_created: 2020-06-14T22:00:49Z
date_published: 2020-08-01T00:00:00Z
date_updated: 2023-08-21T08:25:31Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.tins.2020.05.004
ec_funded: 1
external_id:
isi:
- '000553090600008'
pmid:
- '32507511'
file:
- access_level: open_access
checksum: 67db0251b1d415ae59005f876fcf9e34
content_type: application/pdf
creator: dernst
date_created: 2020-11-25T09:43:40Z
date_updated: 2020-11-25T09:43:40Z
file_id: '8805'
file_name: 2020_TrendsNeuroscience_Parenti.pdf
file_size: 1439550
relation: main_file
success: 1
file_date_updated: 2020-11-25T09:43:40Z
has_accepted_license: '1'
intvolume: ' 43'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 608-621
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
publication: Trends in Neurosciences
publication_identifier:
eissn:
- 1878108X
issn:
- '01662236'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Neurodevelopmental disorders: From genetics to functional pathways'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 43
year: '2020'
...
---
_id: '7149'
abstract:
- lang: eng
text: In recent years, many genes have been associated with chromatinopathies classified
as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these
patients becomes less recognizable, overlapping to features characteristic of
other syndromes caused by genetic variants affecting different regulators of chromatin
structure and function. Therefore, Cornelia de Lange syndrome diagnosis might
be arduous due to the seldom discordance between unexpected molecular diagnosis
and clinical evaluation. Here, we review the molecular features of Cornelia de
Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part
of a larger “rare disease family” sharing multiple clinical features and common
disrupted molecular pathways.
acknowledgement: ' Dipartimento DiSS, Università degli Studi di Milano, Grant/Award
Number: Linea 2; Fondazione Cariplo, Grant/Award Number: 2015-0783; German Federal
Ministry of Education and Research (BMBF), Grant/Award Number: CHROMATIN-Net; Medical
Faculty of the University of Lübeck, Grant/Award Number: J09-2017; Nickel & Co S.p.A.;
Università degli Studi di Milano, Grant/Award Numbers: Molecular & Translational
Medicine PhD Scholarship, Translational Medicine PhD Scholarship'
article_processing_charge: No
article_type: review
author:
- first_name: Laura
full_name: Avagliano, Laura
last_name: Avagliano
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Paolo
full_name: Grazioli, Paolo
last_name: Grazioli
- first_name: Elisabetta
full_name: Di Fede, Elisabetta
last_name: Di Fede
- first_name: Chiara
full_name: Parodi, Chiara
last_name: Parodi
- first_name: Milena
full_name: Mariani, Milena
last_name: Mariani
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Angelo
full_name: Selicorni, Angelo
last_name: Selicorni
- first_name: Cristina
full_name: Gervasini, Cristina
last_name: Gervasini
- first_name: Valentina
full_name: Massa, Valentina
last_name: Massa
citation:
ama: 'Avagliano L, Parenti I, Grazioli P, et al. Chromatinopathies: A focus on Cornelia
de Lange syndrome. Clinical Genetics. 2020;97(1):3-11. doi:10.1111/cge.13674'
apa: 'Avagliano, L., Parenti, I., Grazioli, P., Di Fede, E., Parodi, C., Mariani,
M., … Massa, V. (2020). Chromatinopathies: A focus on Cornelia de Lange syndrome.
Clinical Genetics. Wiley. https://doi.org/10.1111/cge.13674'
chicago: 'Avagliano, Laura, Ilaria Parenti, Paolo Grazioli, Elisabetta Di Fede,
Chiara Parodi, Milena Mariani, Frank J. Kaiser, Angelo Selicorni, Cristina Gervasini,
and Valentina Massa. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.”
Clinical Genetics. Wiley, 2020. https://doi.org/10.1111/cge.13674.'
ieee: 'L. Avagliano et al., “Chromatinopathies: A focus on Cornelia de Lange
syndrome,” Clinical Genetics, vol. 97, no. 1. Wiley, pp. 3–11, 2020.'
ista: 'Avagliano L, Parenti I, Grazioli P, Di Fede E, Parodi C, Mariani M, Kaiser
FJ, Selicorni A, Gervasini C, Massa V. 2020. Chromatinopathies: A focus on Cornelia
de Lange syndrome. Clinical Genetics. 97(1), 3–11.'
mla: 'Avagliano, Laura, et al. “Chromatinopathies: A Focus on Cornelia de Lange
Syndrome.” Clinical Genetics, vol. 97, no. 1, Wiley, 2020, pp. 3–11, doi:10.1111/cge.13674.'
short: L. Avagliano, I. Parenti, P. Grazioli, E. Di Fede, C. Parodi, M. Mariani,
F.J. Kaiser, A. Selicorni, C. Gervasini, V. Massa, Clinical Genetics 97 (2020)
3–11.
date_created: 2019-12-04T16:10:59Z
date_published: 2020-01-01T00:00:00Z
date_updated: 2023-08-17T14:06:20Z
day: '01'
department:
- _id: GaNo
doi: 10.1111/cge.13674
external_id:
isi:
- '000562561800001'
pmid:
- '31721174'
intvolume: ' 97'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: 3-11
pmid: 1
publication: Clinical Genetics
publication_identifier:
eissn:
- 1399-0004
issn:
- 0009-9163
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Chromatinopathies: A focus on Cornelia de Lange syndrome'
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 97
year: '2020'
...
---
_id: '7488'
abstract:
- lang: eng
text: Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is
associated with a recognisable facial pattern. However, the heterogeneity in causal
genes and the presence of overlapping syndromes have made it increasingly difficult
to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene,
is having a growing impact on the diagnosis and management of genetic diseases
by analysing the features of affected individuals. Here, we performed a phenotypic
study on a cohort of 49 individuals harbouring causative variants in known CdLS
genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis
of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within
the top five predicted syndromes for 97.9% of our cases and even listed as first
prediction for 83.7%. The age of patients did not seem to affect the prediction
accuracy, whereas our results indicate a correlation between the clinical score
and affected genes. Furthermore, each gene presents a different pattern recognition
that may be used to develop new neural networks with the goal of separating different
genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis
based on deep learning could support the clinical diagnosis of CdLS.
article_number: '1042'
article_processing_charge: No
article_type: original
author:
- first_name: Ana
full_name: Latorre-Pellicer, Ana
last_name: Latorre-Pellicer
- first_name: Ángela
full_name: Ascaso, Ángela
last_name: Ascaso
- first_name: Laura
full_name: Trujillano, Laura
last_name: Trujillano
- first_name: Marta
full_name: Gil-Salvador, Marta
last_name: Gil-Salvador
- first_name: Maria
full_name: Arnedo, Maria
last_name: Arnedo
- first_name: Cristina
full_name: Lucia-Campos, Cristina
last_name: Lucia-Campos
- first_name: Rebeca
full_name: Antoñanzas-Pérez, Rebeca
last_name: Antoñanzas-Pérez
- first_name: Iñigo
full_name: Marcos-Alcalde, Iñigo
last_name: Marcos-Alcalde
- first_name: Ilaria
full_name: Parenti, Ilaria
id: D93538B0-5B71-11E9-AC62-02EBE5697425
last_name: Parenti
- first_name: Gloria
full_name: Bueno-Lozano, Gloria
last_name: Bueno-Lozano
- first_name: Antonio
full_name: Musio, Antonio
last_name: Musio
- first_name: Beatriz
full_name: Puisac, Beatriz
last_name: Puisac
- first_name: Frank J.
full_name: Kaiser, Frank J.
last_name: Kaiser
- first_name: Feliciano J.
full_name: Ramos, Feliciano J.
last_name: Ramos
- first_name: Paulino
full_name: Gómez-Puertas, Paulino
last_name: Gómez-Puertas
- first_name: Juan
full_name: Pié, Juan
last_name: Pié
citation:
ama: Latorre-Pellicer A, Ascaso Á, Trujillano L, et al. Evaluating Face2Gene as
a tool to identify Cornelia de Lange syndrome by facial phenotypes. International
Journal of Molecular Sciences. 2020;21(3). doi:10.3390/ijms21031042
apa: Latorre-Pellicer, A., Ascaso, Á., Trujillano, L., Gil-Salvador, M., Arnedo,
M., Lucia-Campos, C., … Pié, J. (2020). Evaluating Face2Gene as a tool to identify
Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms21031042
chicago: Latorre-Pellicer, Ana, Ángela Ascaso, Laura Trujillano, Marta Gil-Salvador,
Maria Arnedo, Cristina Lucia-Campos, Rebeca Antoñanzas-Pérez, et al. “Evaluating
Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.”
International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21031042.
ieee: A. Latorre-Pellicer et al., “Evaluating Face2Gene as a tool to identify
Cornelia de Lange syndrome by facial phenotypes,” International Journal of
Molecular Sciences, vol. 21, no. 3. MDPI, 2020.
ista: Latorre-Pellicer A, Ascaso Á, Trujillano L, Gil-Salvador M, Arnedo M, Lucia-Campos
C, Antoñanzas-Pérez R, Marcos-Alcalde I, Parenti I, Bueno-Lozano G, Musio A, Puisac
B, Kaiser FJ, Ramos FJ, Gómez-Puertas P, Pié J. 2020. Evaluating Face2Gene as
a tool to identify Cornelia de Lange syndrome by facial phenotypes. International
Journal of Molecular Sciences. 21(3), 1042.
mla: Latorre-Pellicer, Ana, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia
de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular
Sciences, vol. 21, no. 3, 1042, MDPI, 2020, doi:10.3390/ijms21031042.
short: A. Latorre-Pellicer, Á. Ascaso, L. Trujillano, M. Gil-Salvador, M. Arnedo,
C. Lucia-Campos, R. Antoñanzas-Pérez, I. Marcos-Alcalde, I. Parenti, G. Bueno-Lozano,
A. Musio, B. Puisac, F.J. Kaiser, F.J. Ramos, P. Gómez-Puertas, J. Pié, International
Journal of Molecular Sciences 21 (2020).
date_created: 2020-02-16T23:00:49Z
date_published: 2020-02-04T00:00:00Z
date_updated: 2023-08-18T06:35:41Z
day: '04'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.3390/ijms21031042
external_id:
isi:
- '000522551606028'
file:
- access_level: open_access
checksum: 0e6658c4fe329d55d4d9bef01c5b15d0
content_type: application/pdf
creator: dernst
date_created: 2020-02-18T07:49:22Z
date_updated: 2020-07-14T12:47:59Z
file_id: '7496'
file_name: 2020_IntMolecSciences_Latorre.pdf
file_size: 4271234
relation: main_file
file_date_updated: 2020-07-14T12:47:59Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '3'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- '14220067'
issn:
- '16616596'
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial
phenotypes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 21
year: '2020'
...