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Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination

Overview of attention for article published in American Journal of Human Genetics, April 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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6 X users
wikipedia
1 Wikipedia page

Citations

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62 Dimensions

Readers on

mendeley
83 Mendeley
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1 CiteULike
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Title
Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination
Published in
American Journal of Human Genetics, April 2015
DOI 10.1016/j.ajhg.2015.03.003
Pubmed ID
Authors

Tojo Nakayama, Almundher Al-Maawali, Malak El-Quessny, Anna Rajab, Samir Khalil, Joan M Stoler, Wen-Hann Tan, Ramzi Nasir, Klaus Schmitz-Abe, R Sean Hill, Jennifer N Partlow, Muna Al-Saffar, Sarah Servattalab, Christopher M LaCoursiere, Dimira E Tambunan, Michael E Coulter, Princess C Elhosary, Grzegorz Gorski, A James Barkovich, Kyriacos Markianos, Annapurna Poduri, Ganeshwaran H Mochida

Abstract

Despite recent advances in understanding the genetic bases of microcephaly, a large number of cases of microcephaly remain unexplained, suggesting that many microcephaly syndromes and associated genes have yet to be identified. Here, we report mutations in PYCR2, which encodes an enzyme in the proline biosynthesis pathway, as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume. Linkage mapping and whole-exome sequencing identified homozygous mutations (c.355C>T [p.Arg119Cys] and c.751C>T [p.Arg251Cys]) in PYCR2 in the affected individuals of two consanguineous families. A lymphoblastoid cell line from one affected individual showed a strong reduction in the amount of PYCR2. When mutant cDNAs were transfected into HEK293FT cells, both variant proteins retained normal mitochondrial localization but had lower amounts than the wild-type protein, suggesting that the variant proteins were less stable. A PYCR2-deficient HEK293FT cell line generated by genome editing with the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system showed that PYCR2 loss of function led to decreased mitochondrial membrane potential and increased susceptibility to apoptosis under oxidative stress. Morpholino-based knockdown of a zebrafish PYCR2 ortholog, pycr1b, recapitulated the human microcephaly phenotype, which was rescued by wild-type human PYCR2 mRNA, but not by mutant mRNAs, further supporting the pathogenicity of the identified variants. Hypomyelination and the absence of lax, wrinkly skin distinguishes this condition from that caused by previously reported mutations in the gene encoding PYCR2's isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 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 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 83 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 23%
Researcher 14 17%
Student > Bachelor 8 10%
Student > Master 8 10%
Other 5 6%
Other 11 13%
Unknown 18 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 23%
Medicine and Dentistry 13 16%
Agricultural and Biological Sciences 13 16%
Neuroscience 6 7%
Pharmacology, Toxicology and Pharmaceutical Science 4 5%
Other 8 10%
Unknown 20 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 31 July 2015.
All research outputs
#5,446,994
of 25,374,647 outputs
Outputs from American Journal of Human Genetics
#2,421
of 5,879 outputs
Outputs of similar age
#64,568
of 279,975 outputs
Outputs of similar age from American Journal of Human Genetics
#28
of 52 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,879 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 gotten more attention than average, scoring higher than 52% 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 279,975 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 52 others from the same source and published within six weeks on either side of this one. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.