12 research outputs found
Mechanisms and Clinical Implications of Human X Chromosome Inactivation
- Author
- Publication venue
- urn:ISBN:978-94-6299-264-1
- Publication date
- 12/01/2016
- Field of study
Buccal swab as a reliable predictor for X inactivation ratio in inaccessible tissues
- Author
- Publication venue
- 'BMJ'
- Publication date
- 28/07/2015
- Field of study
Background As a result of the epigenetic phenomenon of X chromosome inactivation (XCI) every woman is a mosaic of cells with either an inactive paternal X chromosome or an inactive maternal X chromosome. The ratio between inactive paternal and maternal X chromosomes is different for every female individual, and can influence an X-encoded trait or disease. A multitude of X linked conditions is known, and for many of them it is recognised that the phenotype in affected female carriers of the causative mutation is modulated by the XCI ratio. To predict disease severity an XCI ratio is usually determined in peripheral blood samples. However, the correlation between XCI ratios in peripheral blood and disease affected tissues, that are often inaccessible, is poorly understood. Here, we tested several tissues obtained from autopsies of 12 female individuals for patch size and XCI ratio. Methods XCI ratios were analysed using methylsensitive PCR-based assays for the AR, PCSK1N and SLITRK4 loci. XCI patch size was analysed by testing the XCI ratio of tissue samples with decreasing size. Results XCI patch size was analysed for liver, muscle, ovary and brain samples and was found too small to confound testing for XCI ratio in these tissues. XCI ratios were determined in the easily accessible tissues, blood, buccal epithelium and hair follicle, and compared with ratios in several inaccessible tissues. Conclusions Buccal epithelium is preferable over peripheral blood for predicting XCI ratios of inaccessible tissues. Ovary is the only inaccessible tissue showing a poor correlation to blood and buccal epithelium, but has a good correlation to hair follicle instead
Stable X chromosome reactivation in female human induced pluripotent stem cells
- Author
- Barakat T.S. (Tahsin Stefan)
- Boter M. (Marjan)
- Douben H. (Hannie)
- Eussen H.J.F.M.M. (Bert)
- Galjaard R-J.H. (Robert-Jan)
- Ghazvini M. (Mehrnaz)
- Gribnau J.H. (Joost)
- Grootegoed J.A. (Anton)
- Hoon B. (Bas) de
- Klein A. (Annelies) de
- Laven J.S.E. (Joop)
- Li T. (Tracy)
- Van Der Linden R. (Reinier)
- Van Der Stap N. (Nathalie)
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2015
- Field of study
In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female human fibroblasts into induced pluripotent stem cells (iPSCs) leads to reactivation of the inactive X chromosome (Xi), we have generated iPSC lines from fibroblasts heterozygous for large X-chromosomal deletions. These fibroblasts show completely skewed XCI of the mutated X chromosome, enabling monitoring of X chromosome reactivation (XCR) and XCI using allele-specific single-cell expression analysis. This approach revealed that XCR is robust under standard culture conditions, but does not prevent reinitiation of XCI, resulting in a mixed population of cells with either two active X chromosomes (Xas) or one Xa and one Xi. This mixed population of XaXa and XaXi cells is stabilized in naive human stem cell medium, allowing expansion of clones with two Xas
X chromosome inactivation in a female carrier of a 1.28 mb deletion encompassing the human X inactivation centre
- Author
- Publication venue
- 'The Royal Society'
- Publication date
- 05/11/2017
- Field of study
X chromosome inactivation (XCI) is a mechanism specifically initiated in female cells to silence one X chromosome, thereby equalizing the dose of X-linked gene products between male and female cells. XCI is regulated by a locus on the X chromosome termed the X-inactivation centre (XIC). Located within the XIC is XIST, which acts as a m
Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network
- Author
- Abbott R.
- Abe H.
- Acernese F.
- Ackley Kendall
- Adhicary S.
- Adhikari Naresh
- Adhikari Rana X.
- Adkins V. K.
- Adya V. B.
- Affeldt C.
- Agarwal D.
- Agathos Michalis
- Aguiar Odylio D.
- Aiello Lorenzo
- Ain A.
- Ajith Parameswaran
- Akutsu Tomotada
- Albanesi S.
- Alfaidi R. A.
- Allocca Annalisa
- Alléné C.
- Altin Paul
- Amato Alex
- Anand S.
- Ananyeva A.
- Anderson Stuart
- Anderson Warren G.
- Ando M.
- Andrade T.
- Andrea Prodi Giovanni
- Andres Nicolas
- Andric Tomislav
- Andrés-Carcasona Marc
- Anne Bizouard Marie
- Ansoldi S.
- Antelis Javier M.
- Antier Sarah
- Antonio Font Roda Jose
- Apostolatos T.
- Appavuravther E. Z.
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- Arai Koji
- Araya Akito
- Araya Melody
- Areeda Joseph
- Arif Shaikh Md
- Aritomi Naoki
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- Asada Hideki
- Ashton Gregory
- Aso Yoichi
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- Zevin Michael
- Zhan M.
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- Zhao Yue
- Zhao Yuhang
- Zheng Yanyan
- Zhou R.
- Zhu Xingjiang
- Zhu Zong-Hong
- Zimmerman Aaron
- Zucker M. E.
- ĂrpĂĄd Gergely LĂĄszlĂł
- ć ćæŹœ
- æčćšéź
- çè°š
- éœäžž éèĄ
- Publication venue
- Publication date
- 01/04/2023
- Field of study
Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects
Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo
- Author
- Abac A. G.
- Abbott R.
- Abe H.
- Acernese F.
- Ackley Kendall
- Adamcewicz C.
- Adhicary S.
- Adhikari Naresh
- Adhikari Rana X.
- Adkins V. K.
- Adya V. B.
- Affeldt C.
- Afif Ismail M.
- Agarwal D.
- Agathos Michalis
- Aguiar Odylio D.
- Aguilar I.
- Aiello Lorenzo
- Ain Anirban
- Ajith Parameswaran
- Akseli Hannuksela Otto
- Akutsu Tomotada
- Al-Jodah Ammar
- Albanesi S.
- Alberto Trani Alessandro
- Alfaidi Reem Atallah E
- Allocca Annalisa
- Alléné C.
- Almualla M.
- Altin Paul
- Amato Alex
- Amez-Droz L.
- Amorosi A.
- Anand S.
- Ananyeva A.
- Andersen R.
- Anderson Stuart
- Anderson Warren G.
- Andia Manuel
- Ando M.
- Andrade T.
- Andrea Prodi Giovanni
- Andres Nicolas
- Andric Tomislav
- Andrés-Carcasona Marc
- Anne Bizouard Marie
- Ansoldi S.
- Antelis Javier M.
- Antier Sarah
- Antonio Font Roda Jose
- Aoumi M.
- Apostolatos T.
- Appavuravther E. Z.
- Appert S.
- Apple S. K.
- Arai Koji
- Araya Akito
- Araya Melody
- Areeda Joseph
- Arif Shaikh Md
- Aritomi Naoki
- Armato F.
- Arnaud Nicolas
- Arogeti Megan
- Aronson Scott
- Arun K. G.
- Ashton Gregory
- Aso Yoichi
- Assiduo M.
- Aston S. M.
- Astone Pia
- Aubin Florian
- Babak Stanislav
- Badalyan A.
- Badaracco Francesca
- Badger C.
- Bae Sangwook
- Bagnasco Stefano
- Bai Y.
- Baier Jeremy
- Bajpai Rishabh
- Baka T.
- Ball M.
- Ballardin G.
- Ballmer S. W.
- Baltus Grégory
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- Baylor Amanda
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- Bedakihale V. M.
- Beirnaert Freija
- Bejger MichaĆ
- Bell Angus
- Benedetto V.
- Beniwal D.
- Benoit William
- Bentley Joe
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- Bergamin Fabio
- Berger Beverly
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- Berry Christopher P. L.
- Bersanetti Diego
- Bertolini A.
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- LIETO ALBERTO. DI.
- LIGO Collaboration
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- MASCIOLI ADRIANO. FRATTALE.
- Masserot A.
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- MORALES ESTER. RUIZ.
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- PACE SIBILLA. DI.
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- Zweizig John
- Ălvarez-LĂłpez S.
- ĂrpĂĄd Gergely LĂĄszlĂł
- ć ćæŹœ
- æčćšéź
- éœäžž éèĄ
- Publication venue
- Publication date
- 01/08/2023
- Field of study
Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 Mâ) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<eâ€0.3 at 0.33 Gpcâ3 yrâ1 at 90\% confidence level
Ultralight vector dark matter search using data from the KAGRA O3GK run
- Author
- Abac A. G.
- Abbott R.
- Abe H.
- Abouelfettouh I.
- Acernese F.
- Ackley Kendall
- Adamcewicz Christian
- Adhicary S.
- Adhikari Naresh
- Adhikari Rana X.
- Adkins V. K.
- Adya V. B.
- Affeldt C.
- Afif Ismail M.
- Agarwal Deepali
- Agathos Michalis
- Aguiar Odylio D.
- Aguilar I.
- Aiello Lorenzo
- Ain Anirban
- Ajith Parameswaran
- Akseli Hannuksela Otto
- Akutsu Tomotada
- Al-Jodah Ammar
- Al-Shammari S.
- Albanesi S.
- Alberto Trani Alessandro
- Alfaidi Reem Atallah E
- Allocca Annalisa
- Alléné C.
- Altin Paul
- Alvarez-Lopez Sofia
- Amato Alex
- Amez-Droz L.
- Amorosi A.
- Amra C.
- Anand S.
- Ananyeva A.
- Anderson Stuart
- Anderson Warren G.
- Andia Manuel
- Ando M.
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- Andrea Prodi Giovanni
- Andres Nicolas
- Andric Tomislav
- Andrés-Carcasona Marc
- Anglin J.
- Anne Bizouard Marie
- Ansoldi S.
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- Antier Sarah
- Antoni Ramis Vidal Felip
- Antonietta Palaia Maria
- Antonio Font Roda Jose
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- Armato F.
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- de rossi camilla
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- schwartz eyal
- Scott Jamie
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- Seetharamu T. C.
- Seglar-Arroyo Monica
- Sekiguchi Yuichiro
- Sellers D.
- Sengupta Anand
- Sentenac D.
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- Sergeev A.
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- Servignat Gaël
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- Shao Lijing
- Shapiro Key Joey
- Sharan Salafia Om
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- Shawhan Peter
- SHCHEBLANOV Nikita
- Shen B.
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- shimode katsuhiko
- Shinkai Hisa-aki
- Shiota J.
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- SINGH MUKESH. KUMAR.
- Singha Ayatri
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- Somiya Kentaro
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- soni siddharth
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- Sorrentino F.
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- Spencer Andrew
- Spera Mario
- Spinicelli P.
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- Stachurski Federico
- STEER DaniĂšle
- Steffano Bonilla Marceline
- Steinlechner J.
- Steinlechner Sebastian
- Stergioulas Nikolaos
- Stevens P.
- StPierre M.
- Strang L. C.
- Stratta Giulia
- Strong M. D.
- Strunk A.
- Sturani R.
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- Suchenek M.
- Sueltmann N.
- Sullivan Andrew G.
- Sullivan K. D.
- Sun Ling
- Sunil S.
- Sur Ankan
- Suresh Jishnu
- Sutton Patrick
- Suzuki Takamasa
- Suzuki Takanori
- Swinkels Bas L.
- Sylvia Biscoveanu Andrea
- Syx A.
- SzczepaĆczyk Marek
- Szewczyk PaweĆ
- SĂ€nger E. M.
- Sébastien Göttel Alexandre
- Tacca Matteo
- Tagoshi Hideyuki
- Tait Simon
- Tak Lun Tsang Terrence
- Takahashi Hirotaka
- Takahashi Ryutaro
- Takamori Akiteru
- Takatani K.
- Takeda Hiroki
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- Takidera H.
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- Tamaki M.
- Tamanini Nicola
- Tanabe D.
- Tanaka K.
- Tanaka Shuta
- Tanaka Takahiro
- Tanasijczuk A. J.
- Tang D.
- Tanioka Satoshi
- Tanner D. B.
- Tao Liu
- Tapia San MartĂn E. N.
- Tapia R. D.
- Tarafder R.
- Taranto C.
- Taruya Atsushi
- Tasson Jay
- Teloi M.
- Tenorio Rodrigo
- Themann H.
- Theodoropoulos A.
- Thirugnanasambandam M. P.
- Thomas M.
- Thomas P.
- Thompson Jonathan
- Thondapu S. R.
- Thorne K. A.
- Thrane E.
- Tissino Jacopo
- Tiwari A.
- tiwari shubhanshu
- Tiwari Srishti
- tiwari vaibhav
- Todd M. R.
- Toivonen Andrew
- Toland Karl
- Tolley Arthur E.
- Tomita K.
- Tomura Tomonobu
- Tong-Yu C.
- Toriyama A.
- Toropov Nikita
- Torres Forne Alejandro
- Torrie C. I.
- Toscani Martina
- Tosta e Melo Iara
- Tournefier Edwige
- TRAPANANTI Angela
- Travasso Flavio
- Traylor G.
- Trenado Juan
- Trevor M.
- Tripathee Aashish
- Troiano L.
- Trovato Agata
- Trozzo L.
- Trudeau R. J.
- Tso R.
- Tsuchida Satoshi
- Tsukada L.
- Tsutsui Takuya
- Turbang Kevin
- Turconi Margherita
- Turski C.
- Ubach Helena
- Ubhi A. S.
- Uchiyama Takashi
- Udall Rhiannon
- Uehara Tomoyuki
- Ueno Koh
- Unnikrishnan C. S.
- Ushiba Takafumi
- Vacatello Michele
- Vahlbruch Henning
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- Vajpeyi A.
- Valdes Guillermo
- Valencia J.
- Valentini Michele
- Vallejo-Peña S. A.
- Vallero S.
- Valsan Vinaya
- Valérie Martinez
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- van Beuzekom Martin
- van Dael Mathyn
- Van de Walle A.
- van den Brand Johannes
- Van Den Broeck C.
- van der Sluys Marc
- van Dongen Jesse
- Van Haevermaet Hans
- van Heijningen Joris
- van Putten Maurice
- Van Ranst Zeb
- van Remortel Nick
- Vander-Hyde D. C.
- Vandra K.
- Vanosky J.
- Vardaro M.
- Vargas A. F.
- varma vijay
- Vasuth Matyas
- vecchio alberto
- Vedovato G.
- Veitch John
- Veitch Peter
- Venikoudis S.
- Venneberg Jasper
- Verdier Patrice
- Verkindt Didier
- Verma B.
- Verma P.
- Verma Yogesh
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- Veske DoÄa
- Vetrano F.
- Veutro A.
- Vibhute Ajay
- Viceré Andrea
- Vidyant S.
- Viets Aaron
- Vijaykumar Aditya
- Vilkha A.
- Villa-Ortega VerĂłnica
- Vincent Erin
- Vinet J. -Y.
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- Virgo Collaboration
- Virtuoso Andrea
- Vitale Salvatore
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- Voigt Daniel
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- Wade Madeline
- Wagner Katelyn
- Walet R. C.
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- Waratkar Gaurav
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- Washimi Tatsuki
- Washington N. Y.
- Watarai D.
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- Weaving C. R.
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- Weinert M.
- Weinstein Alan J.
- Weiss R.
- Weizmann Kiendrebeogo R.
- Weller C. M.
- Weller Robert
- Wellmann F.
- Wen L.
- Wette Karl
- WeĂels P.
- Whelan John
- White D. D.
- Whiting Bernard F.
- Whittle Chris
- Wildberger J. B.
- Wilk O. S.
- Wilken Dennis
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- Woan Graham
- Woehler J.
- Wofford Jared
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- Wong Henry T.
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- Wright Mick
- Wu Chien-Ming
- Wu David S.
- Wu Hsun-Chung
- Wysocki Daniel
- Xiao Liting
- Xu Victoria
- Xu Yumeng
- Yaala M. Ben
- Yadav Nikesh
- Yakovlev Alexey
- Yamamoto Hiroaki
- Yamamoto Kazuhiro
- Yamamoto M.
- Yamamoto Takahiro
- Yamamoto Takahiro S.
- Yamamura S.
- Yamazaki Ryo
- Yan S.
- Yan T.
- Yang F.
- Yang Fengwei
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- Yang Yi
- Yarbrough Zach
- Yeh S. -W.
- Yelikar A. B.
- Yeung S. M. C.
- Yin X.
- Yokoyama Jun'ichi
- Yokozawa T.
- Yoo Jooheon
- Yu Hang
- Yuzurihara Hirotaka
- ZadroĆŒny A.
- Zahoor Jan Aasim
- Zannelli A. J.
- Zanolin M.
- Zeeshan M.
- Zelenova T.
- Zendri J. -P.
- Zeoli M.
- Zerrad M.
- Zevin Michael
- Zhang A. C.
- Zhang Jue
- Zhang L.
- Zhang Rui
- Zhang T.
- Zhang Ya
- Zhao C.
- Zhao Yue
- Zhao Yuhang
- Zheng Yanyan
- Zhong Haowen
- Zhong S.
- Zhou R.
- Zhu Zong-Hong
- Zucker M. E.
- Zweizig John
- ĂrpĂĄd Gergely LĂĄszlĂł
- ć ćæŹœ
- æčćšéź
- éœäžž éèĄ
- Publication venue
- Publication date
- 01/03/2024
- Field of study
Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)BâL gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)BâL gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM
Fitting the Puzzle Pieces: The Bigger Picture of XCI
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/02/2016
- Field of study
X chromosome inactivation (XCI) is a mammalian-specific process initiated in all female cells, leading to one inactivated X chromosome. The robust nature of XCI, and the complex mechanisms involved in directing this process, makes XCI an important model system to study all aspects of gene regulation. XCI is divided into distinct phases: initiation, establishment, and maintenance of the inactive X (Xi). Recent studies shed important new light on the mechanisms directing all three phases of XCI. These findings include new regulatory pathways in XCI initiation, and the identification of a plethora of new factors involved in establishing and maintaining the Xi. In this review, we will highlight and discuss these new findings in the bigger picture of XCI
Impact of intertumoral heterogeneity on predicting chemotherapy response of BRCA1-deficient mammary tumors
- Author
- Borst P. (Piet)
- Burg E. (Eline) van der
- Gillet J.-P. (Jean-Pierre)
- Gottesman R.F. (Rebecca)
- Gribnau J.H. (Joost)
- Hoon B. (Bas) de
- Jaspers J.E. (Janneke)
- Jonkers J. (Jos)
- Jonkers M. (Martijn)
- Kersbergen A. (Ariena)
- Linn S.C. (Sabine)
- Lodén M. (Martin)
- Pajic M. (Marina)
- Ronde J. (Jorma) de
- Rottenberg S. (Sven)
- Schouten P.C. (Philip)
- Sol W. (Wendy)
- Vollebergh M.A. (Marieke)
- Wesseling J. (Jelle)
- Wessels L. (Lodewyk)
- Zander A.R.
- Publication venue
- 'American Association for Cancer Research (AACR)'
- Publication date
- 01/05/2012
- Field of study
The lack of markers to predict chemotherapy responses in patients poses a major handicap in cancer treatment. We searched for gene expression patterns that correlate with docetaxel or cisplatin response in a mouse model for breast cancer associated with BRCA1 deficiency. Array-based expression profiling did not identify a single marker gene predicting docetaxel response, despite an increase in Abcb1 (P-glycoprotein) expression that was sufficient to explain resistance in several poor responders. Intertumoral heterogeneity explained the inability to identify a predictive gene expression signature for docetaxel. To address this problem, we used a novel algorithm designed to detect differential gene expression in a subgroup of the poor responders that could identify tumors with increased Abcb1 transcript levels. In contrast, standard analytical tools, such as significance analysis of microarrays, detected a marker only if it correlated with response in a substantial fraction of tumors. For example, low expression of the Xist gene correlated with cisplatin hypersensitivity in most tumors, and it also predicted long recurrence-free survival of HER2-negative, stage III breast cancer patients treated with intensive platinum-based chemotherapy. Our findings may prove useful for selecting patients with high-risk breast cancer who could benefit from platinum-based therapy
Pathogenic variants in E3 ubiquitin ligase RLIM/RNF12 lead to a syndromic X-linked intellectual disability and behavior disorder
- Author
- A Trockenbacher
- A Upadhyay
- AK Emde
- Andreas Dufke
- Annick Toutain
- AT Vulto-van Silfhout
- Aysegul Ozanturk
- B Budny
- B Jiao
- Bas de Hoon
- Benjamin J. Kelly
- BS Pickard
- C Erbel-Sieler
- C Ganos
- C Gontan
- C Gontan
- C Lavedan
- Christelle Golzio
- Christopher Schroeder
- Claudia Bauer
- Cristina Gontan
- CS Hill
- CS Hwang
- D Weese
- Daniel C Koboldt
- DH Margolin
- DM Haddad
- E Flex
- E Tonne
- Eric Haan
- Eveline Rentmeester
- G Froyen
- G Froyen
- G Rodriguez Criado
- GermĂĄn RodrĂguez Criado
- H Hu
- Hans-Hilger Ropers
- Hao Hu
- HM Emmerton-Coughlin
- HP Ostendorff
- HP Ostendorff
- HP Ostendorff
- I Bach
- I Bach
- I Hiratani
- I Jonkers
- I Papangeli
- J Shin
- J Shin
- J So
- J Vandewalle
- J Zhang
- J Zhang
- Jan Liebelt
- Jean-Pierre Fryns
- Joep Geraedts
- Joost Gribnau
- Joris Vermeesch
- Jozef Gecz
- JS Witteveen
- K Gao
- K Mesbah
- K Retterer
- Karen W. Gripp
- Kathryn Friend
- Kees E. P. van Roozendaal
- KM Bone
- Koen Devriendt
- L Basel-Vanagaite
- L Carrel
- L Sha
- L Yu
- L Yu
- L Zhang
- LE Jao
- LG Nucifora
- Lucinda Murray
- Lynne Hobson
- M Alqwaifly
- M Badura-Stronka
- M Gabriele
- M Ishibashi
- M Isrie
- M Kelly
- M Longoni
- M Longoni
- M Sukalo
- M Weider
- M Zenker
- MA Ferreira
- Marie Shaw
- Marjan De Rademaeker
- Martine Raynaud
- Michael Field
- MJ Moen
- Molka Kammoun
- MY Son
- NA Quaderi
- NC Bramswig
- Nicholas Katsanis
- OH Kramer
- Olaf Riess
- P Navarro
- P Santens
- Peter Bauer
- Peter White
- PJ Marie
- PK Donahoe
- PS Tarpey
- R Gao
- R Kumar
- R Rossetti
- RC Allen
- Renee Carroll
- RM Nascimento
- RN Wang
- S Retaux
- S Schweiger
- S Stricker
- S Zhou
- SA Johnsen
- Scott E. Hickey
- SG Frints
- Stefan A. Haas
- Sungjin Moon
- Suzanna G. M. Frints
- SV Mullegama
- Sylvie Manouvrier-Hanu
- T Kishino
- Theresa Mihalic Mosher
- TS Barakat
- Ute Grasshoff
- V des Portes
- Vera M. Kalscheuer
- X Chen
- X Yingjun
- Y Huang
- Y Zou
- YR Her
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 04/05/2018
- Field of study
RLIM, also known as RNF12, is an X-linked E3 ubiquitin ligase acting as a negative regulator of LIM-domain containing transcription factors and participates in X-chromosome inactivation (XCI) in mice. We report the genetic and clinical findings of 84 individuals from nine unrelated families, eight of whom who have pathogenic variants in RLIM (RING finger LIM domain-interacting protein). A total of 40 affected males have X-linked intellectual disability (XLID) and variable behavioral anomalies with or without congenital malformations. In contrast, 44 heterozygous female carriers have normal cognition and behavior, but eight showed mild physical features. All RLIM variants identified are missense changes co-segregating with the phenotype and predicted to affect protein function. Eight of the nine altered amino acids are conserved and lie either within a domain essential for binding interacting proteins or in the C-terminal RING finger catalytic domain. In vitro experiments revealed that these amino acid changes in the RLIM RING finger impaired RLIM ubiquitin ligase activity. In vivo experiments in rlim mutant zebrafish showed that wild type RLIM rescued the zebrafish rlim phenotype, whereas the patient-specific missense RLIM variants failed to rescue the phenotype and thus represent likely severe loss-of-function mutations. In summary, we identified a spectrum of RLIM missense variants causing syndromic XLID and affecting the ubiquitin ligase activity of RLIM, suggesting that enzymatic activity of RLIM is required for normal development, cognition and behavior