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Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling

Overview of attention for article published in American Journal of Human Genetics, July 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • Good Attention Score compared to outputs of the same age and source (76th percentile)

Mentioned by

news
1 news outlet
blogs
1 blog
twitter
24 X users
facebook
1 Facebook page
wikipedia
1 Wikipedia page

Citations

dimensions_citation
218 Dimensions

Readers on

mendeley
286 Mendeley
citeulike
1 CiteULike
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Title
Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling
Published in
American Journal of Human Genetics, July 2015
DOI 10.1016/j.ajhg.2015.07.004
Pubmed ID
Authors

Lot Snijders Blok, Erik Madsen, Jane Juusola, Christian Gilissen, Diana Baralle, Margot R.F. Reijnders, Hanka Venselaar, Céline Helsmoortel, Megan T. Cho, Alexander Hoischen, Lisenka E.L.M. Vissers, Tom S. Koemans, Willemijn Wissink-Lindhout, Evan E. Eichler, Corrado Romano, Hilde Van Esch, Connie Stumpel, Maaike Vreeburg, Eric Smeets, Karin Oberndorff, Bregje W.M. van Bon, Marie Shaw, Jozef Gecz, Eric Haan, Melanie Bienek, Corinna Jensen, Bart L. Loeys, Anke Van Dijck, A. Micheil Innes, Hilary Racher, Sascha Vermeer, Nataliya Di Donato, Andreas Rump, Katrina Tatton-Brown, Michael J. Parker, Alex Henderson, Sally A. Lynch, Alan Fryer, Alison Ross, Pradeep Vasudevan, Usha Kini, Ruth Newbury-Ecob, Kate Chandler, Alison Male, the DDD Study, Sybe Dijkstra, Jolanda Schieving, Jacques Giltay, Koen L.I. van Gassen, Janneke Schuurs-Hoeijmakers, Perciliz L. Tan, Igor Pediaditakis, Stefan A. Haas, Kyle Retterer, Patrick Reed, Kristin G. Monaghan, Eden Haverfield, Marvin Natowicz, Angela Myers, Michael C. Kruer, Quinn Stein, Kevin A. Strauss, Karlla W. Brigatti, Katherine Keating, Barbara K. Burton, Katherine H. Kim, Joel Charrow, Jennifer Norman, Audrey Foster-Barber, Antonie D. Kline, Amy Kimball, Elaine Zackai, Margaret Harr, Joyce Fox, Julie McLaughlin, Kristin Lindstrom, Katrina M. Haude, Kees van Roozendaal, Han Brunner, Wendy K. Chung, R. Frank Kooy, Rolph Pfundt, Vera Kalscheuer, Sarju G. Mehta, Nicholas Katsanis, Tjitske Kleefstra

Abstract

Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common causes of ID, accounting for 1%-3% of unexplained ID in females. Although no de novo DDX3X mutations were identified in males, we present three families with segregating missense mutations in DDX3X, suggestive of an X-linked recessive inheritance pattern. In these families, all males with the DDX3X variant had ID, whereas carrier females were unaffected. To explore the pathogenic mechanisms accounting for the differences in disease transmission and phenotype between affected females and affected males with DDX3X missense variants, we used canonical Wnt defects in zebrafish as a surrogate measure of DDX3X function in vivo. We demonstrate a consistent loss-of-function effect of all tested de novo mutations on the Wnt pathway, and we further show a differential effect by gender. The differential activity possibly reflects a dose-dependent effect of DDX3X expression in the context of functional mosaic females versus one-copy males, which reflects the complex biological nature of DDX3X mutations.

X Demographics

X Demographics

The data shown below were collected from the profiles of 24 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 286 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Italy 1 <1%
Brazil 1 <1%
Unknown 283 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 46 16%
Student > Ph. D. Student 44 15%
Student > Master 39 14%
Student > Bachelor 31 11%
Student > Doctoral Student 16 6%
Other 38 13%
Unknown 72 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 74 26%
Agricultural and Biological Sciences 47 16%
Medicine and Dentistry 37 13%
Neuroscience 24 8%
Immunology and Microbiology 6 2%
Other 26 9%
Unknown 72 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 28. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 June 2022.
All research outputs
#1,390,670
of 25,373,627 outputs
Outputs from American Journal of Human Genetics
#741
of 5,878 outputs
Outputs of similar age
#17,419
of 274,988 outputs
Outputs of similar age from American Journal of Human Genetics
#10
of 43 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,878 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.3. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 274,988 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 93% of its contemporaries.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.