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De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome

Overview of attention for article published in American Journal of Human Genetics, December 2015
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  • Above-average Attention Score compared to outputs of the same age (53rd percentile)

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Citations

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38 Dimensions

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51 Mendeley
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Title
De Novo GMNN Mutations Cause Autosomal-Dominant Primordial Dwarfism Associated with Meier-Gorlin Syndrome
Published in
American Journal of Human Genetics, December 2015
DOI 10.1016/j.ajhg.2015.11.006
Pubmed ID
Authors

Lindsay C. Burrage, Wu-Lin Charng, Mohammad K. Eldomery, Jason R. Willer, Erica E. Davis, Dorien Lugtenberg, Wenmiao Zhu, Magalie S. Leduc, Zeynep C. Akdemir, Mahshid Azamian, Gladys Zapata, Patricia P. Hernandez, Jeroen Schoots, Sonja A. de Munnik, Ronald Roepman, Jillian N. Pearring, Shalini Jhangiani, Nicholas Katsanis, Lisenka E.L.M. Vissers, Han G. Brunner, Arthur L. Beaudet, Jill A. Rosenfeld, Donna M. Muzny, Richard A. Gibbs, Christine M. Eng, Fan Xia, Seema R. Lalani, James R. Lupski, Ernie M.H.F. Bongers, Yaping Yang

Abstract

Meier-Gorlin syndrome (MGS) is a genetically heterogeneous primordial dwarfism syndrome known to be caused by biallelic loss-of-function mutations in one of five genes encoding pre-replication complex proteins: ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in these genes cause disruption of the origin of DNA replication initiation. To date, only an autosomal-recessive inheritance pattern has been described in individuals with this disorder, with a molecular etiology established in about three-fourths of cases. Here, we report three subjects with MGS and de novo heterozygous mutations in the 5' end of GMNN, encoding the DNA replication inhibitor geminin. We identified two truncating mutations in exon 2 (the 1(st) coding exon), c.16A>T (p.Lys6(∗)) and c.35_38delTCAA (p.Ile12Lysfs(∗)4), and one missense mutation, c.50A>G (p.Lys17Arg), affecting the second-to-last nucleotide of exon 2 and possibly RNA splicing. Geminin is present during the S, G2, and M phases of the cell cycle and is degraded during the metaphase-anaphase transition by the anaphase-promoting complex (APC), which recognizes the destruction box sequence near the 5' end of the geminin protein. All three GMNN mutations identified alter sites 5' to residue Met28 of the protein, which is located within the destruction box. We present data supporting a gain-of-function mechanism, in which the GMNN mutations result in proteins lacking the destruction box and hence increased protein stability and prolonged inhibition of replication leading to autosomal-dominant MGS.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 51 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
China 1 2%
Unknown 50 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 18%
Student > Master 8 16%
Researcher 7 14%
Student > Bachelor 4 8%
Professor 4 8%
Other 9 18%
Unknown 10 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 16 31%
Medicine and Dentistry 8 16%
Agricultural and Biological Sciences 6 12%
Neuroscience 3 6%
Immunology and Microbiology 2 4%
Other 3 6%
Unknown 13 25%

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 28 June 2016.
All research outputs
#9,703,769
of 16,534,657 outputs
Outputs from American Journal of Human Genetics
#4,342
of 4,930 outputs
Outputs of similar age
#169,426
of 370,550 outputs
Outputs of similar age from American Journal of Human Genetics
#42
of 45 outputs
Altmetric has tracked 16,534,657 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 4,930 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.5. 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 370,550 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 53% of its contemporaries.
We're also able to compare this research output to 45 others from the same source and published within six weeks on either side of this one. This one is in the 6th percentile – i.e., 6% of its contemporaries scored the same or lower than it.