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ZC4H2 Mutations Are Associated with Arthrogryposis Multiplex Congenita and Intellectual Disability through Impairment of Central and Peripheral Synaptic Plasticity

Overview of attention for article published in American Journal of Human Genetics, May 2013
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2 tweeters

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Title
ZC4H2 Mutations Are Associated with Arthrogryposis Multiplex Congenita and Intellectual Disability through Impairment of Central and Peripheral Synaptic Plasticity
Published in
American Journal of Human Genetics, May 2013
DOI 10.1016/j.ajhg.2013.03.021
Pubmed ID
Authors

Hiromi Hirata, Indrajit Nanda, Anne van Riesen, Gai McMichael, Hao Hu, Melanie Hambrock, Marie-Amélie Papon, Ute Fischer, Sylviane Marouillat, Can Ding, Servane Alirol, Melanie Bienek, Sabine Preisler-Adams, Astrid Grimme, Dominik Seelow, Richard Webster, Eric Haan, Alastair MacLennan, Werner Stenzel, Tzu Ying Yap, Alison Gardner, Lam Son Nguyen, Marie Shaw, Nicolas Lebrun, Stefan A. Haas, Wolfram Kress, Thomas Haaf, Elke Schellenberger, Jamel Chelly, Géraldine Viot, Lisa G. Shaffer, Jill A. Rosenfeld, Nancy Kramer, Rena Falk, Dima El-Khechen, Luis F. Escobar, Raoul Hennekam, Peter Wieacker, Christoph Hübner, Hans-Hilger Ropers, Jozef Gecz, Markus Schuelke, Frédéric Laumonnier, Vera M. Kalscheuer

Abstract

Arthrogryposis multiplex congenita (AMC) is caused by heterogeneous pathologies leading to multiple antenatal joint contractures through fetal akinesia. Understanding the pathophysiology of this disorder is important for clinical care of the affected individuals and genetic counseling of the families. We thus aimed to establish the genetic basis of an AMC subtype that is associated with multiple dysmorphic features and intellectual disability (ID). We used haplotype analysis, next-generation sequencing, array comparative genomic hybridization, and chromosome breakpoint mapping to identify the pathogenic mutations in families and simplex cases. Suspected disease variants were verified by cosegregation analysis. We identified disease-causing mutations in the zinc-finger gene ZC4H2 in four families affected by X-linked AMC plus ID and one family affected by cerebral palsy. Several heterozygous females were also affected, but to a lesser degree. Furthermore, we found two ZC4H2 deletions and one rearrangement in two female and one male unrelated simplex cases, respectively. In mouse primary hippocampal neurons, transiently produced ZC4H2 localized to the postsynaptic compartment of excitatory synapses, and the altered protein influenced dendritic spine density. In zebrafish, antisense-morpholino-mediated zc4h2 knockdown caused abnormal swimming and impaired α-motoneuron development. All missense mutations identified herein failed to rescue the swimming defect of zebrafish morphants. We conclude that ZC4H2 point mutations, rearrangements, and small deletions cause a clinically variable broad-spectrum neurodevelopmental disorder of the central and peripheral nervous systems in both familial and simplex cases of both sexes. Our results highlight the importance of ZC4H2 for genetic testing of individuals presenting with ID plus muscle weakness and minor or major forms of AMC.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Argentina 1 1%
Unknown 67 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 23%
Student > Master 15 22%
Researcher 12 17%
Other 7 10%
Professor 5 7%
Other 14 20%
Readers by discipline Count As %
Medicine and Dentistry 25 36%
Agricultural and Biological Sciences 15 22%
Biochemistry, Genetics and Molecular Biology 7 10%
Unspecified 7 10%
Neuroscience 5 7%
Other 10 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 21 May 2013.
All research outputs
#6,945,968
of 12,084,702 outputs
Outputs from American Journal of Human Genetics
#3,818
of 4,354 outputs
Outputs of similar age
#62,322
of 130,758 outputs
Outputs of similar age from American Journal of Human Genetics
#43
of 47 outputs
Altmetric has tracked 12,084,702 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,354 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.1. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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 130,758 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 47 others from the same source and published within six weeks on either side of this one. This one is in the 8th percentile – i.e., 8% of its contemporaries scored the same or lower than it.