↓ Skip to main content

Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel–Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects

Overview of attention for article published in Human Molecular Genetics, January 2013
Altmetric Badge

Mentioned by

f1000
1 research highlight platform

Citations

dimensions_citation
89 Dimensions

Readers on

mendeley
95 Mendeley
citeulike
1 CiteULike
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel–Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects
Published in
Human Molecular Genetics, January 2013
DOI 10.1093/hmg/dds546
Pubmed ID
Authors

Zakia A. Abdelhamed, Gabrielle Wheway, Katarzyna Szymanska, Subaashini Natarajan, Carmel Toomes, Chris Inglehearn, Colin A. Johnson

Abstract

The ciliopathies are a group of heterogeneous diseases with considerable variations in phenotype for allelic conditions such as Meckel-Gruber syndrome (MKS) and Joubert syndrome (JBTS) even at the inter-individual level within families. In humans, mutations in TMEM67 (also known as MKS3) cause both MKS and JBTS, with TMEM67 encoding the orphan receptor meckelin (TMEM67) that localizes to the ciliary transition zone. We now describe the Tmem67(tm1(Dgen/H)) knockout mouse model that recapitulates the brain phenotypic variability of these human ciliopathies, with categorization of Tmem67 mutant animals into two phenotypic groups. An MKS-like incipient congenic group (F6 to F10) manifested very variable neurological features (including exencephaly, and frontal/occipital encephalocele) that were associated with the loss of primary cilia, diminished Shh signalling and dorsalization of the caudal neural tube. The 'MKS-like' group also had high de-regulated canonical Wnt/β-catenin signalling associated with hyper-activated Dishevelled-1 (Dvl-1) localized to the basal body. Conversely, a second fully congenic group (F > 10) had less variable features pathognomonic for JBTS (including cerebellar hypoplasia), and retention of abnormal bulbous cilia associated with mild neural tube ventralization. The 'JBTS-like' group had de-regulated low levels of canonical Wnt signalling associated with the loss of Dvl-1 localization to the basal body. Our results suggest that modifier alleles partially determine the variation between MKS and JBTS, implicating the interaction between Dvl-1 and meckelin, or other components of the ciliary transition zone. The Tmem67(tm1(Dgen/H)) line is unique in modelling the variable expressivity of phenotypes in these two ciliopathies.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 95 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 2 2%
United Kingdom 1 1%
United States 1 1%
Germany 1 1%
Unknown 90 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 26 27%
Researcher 19 20%
Student > Bachelor 16 17%
Student > Master 6 6%
Student > Doctoral Student 4 4%
Other 15 16%
Unknown 9 9%
Readers by discipline Count As %
Agricultural and Biological Sciences 36 38%
Biochemistry, Genetics and Molecular Biology 24 25%
Neuroscience 8 8%
Medicine and Dentistry 7 7%
Chemistry 2 2%
Other 5 5%
Unknown 13 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 March 2013.
All research outputs
#17,285,668
of 25,373,627 outputs
Outputs from Human Molecular Genetics
#6,956
of 8,251 outputs
Outputs of similar age
#193,573
of 288,946 outputs
Outputs of similar age from Human Molecular Genetics
#61
of 77 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,251 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.3. This one is in the 10th percentile – i.e., 10% 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 288,946 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 23rd percentile – i.e., 23% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 77 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.