ArticlePLoS genetics2014
An ARHGEF10 deletion is highly associated with a juvenile-onset inherited polyneuropathy in Leonberger and Saint Bernard dogs.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- An Overview of Canine Inherited Neurological Disorders with Known Causal Variants.Animals : an open access journal from MDPI · 2023Review
- Canine models of Charcot-Marie-Tooth: MTMR2, MPZ, and SH3TC2 variants in golden retrievers with congenital hypomyelinating polyneuropathy.Neuromuscular disorders : NMD · 2023Article
- Article
- ARHGEF-10 gene mutation presenting as orbital inflammatory syndrome.BMJ case reports · 2022Article
- Neuropathy-causing TRPV4 mutations disrupt TRPV4-RhoA interactions and impair neurite extension.Nature communications · 2021Article
- AGenes · 2020Article
- Juvenile-onset motor polyneuropathy in Siberian cats.Journal of veterinary internal medicine · 2020Article
- Genomic diversity and population structure of the Leonberger dog breed.Genetics, selection, evolution : GSE · 2020Article
- A RAPGEF6 variant constitutes a major risk factor for laryngeal paralysis in dogs.PLoS genetics · 2019Article
- Involvement of ARHGEF10, GEF for RhoA, in Rab6/Rab8-mediating membrane traffic.Small GTPases · 2019Review
- Canine neuropathies: powerful spontaneous models for human hereditary sensory neuropathies.Human genetics · 2019Review
- Regulators of Rho GTPases in the Nervous System: Molecular Implication in Axon Guidance and Neurological Disorders.International journal of molecular sciences · 2019Review
- Charcot-Marie-Tooth type 4B2 demyelinating neuropathy in miniature Schnauzer dogs caused by a novel splicingPeerJ · 2019Article
- The Dog Model in the Spotlight: Legacy of a Trustful Cooperation.Journal of neuromuscular diseases · 2019Article
- Juvenile-onset polyneuropathy in American Staffordshire Terriers.Journal of veterinary internal medicine · 2018Article
- Canine NAPEPLD-associated models of human myelin disorders.Scientific reports · 2018Article
- Article
- Re-emergence of hereditary polyneuropathy in Scandinavian Alaskan malamute dogs-old enemy or new entity? A case series.Acta veterinaria Scandinavica · 2017Article
- Genetic heterogeneity of motor neuropathies.Neurology · 2017Article
- Genome-Wide Association of Heroin Dependence in Han Chinese.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
An inherited polyneuropathy (PN) observed in Leonberger dogs has clinical similarities to a genetically heterogeneous group of peripheral neuropathies termed Charcot-Marie-Tooth (CMT) disease in humans. The Leonberger disorder is a severe, juvenile-onset, chronic, progressive, and mixed PN, characterized by exercise intolerance, gait abnormalities and muscle atrophy of the pelvic limbs, as well as inspiratory stridor and dyspnea. We mapped a PN locus in Leonbergers to a 250 kb region on canine chromosome 16 (Praw = 1.16×10-10, Pgenome, corrected = 0.006) utilizing a high-density SNP array. Within this interval is the ARHGEF10 gene, a member of the rho family of GTPases known to be involved in neuronal growth and axonal migration, and implicated in human hypomyelination. ARHGEF10 sequencing identified a 10 bp deletion in affected dogs that removes four nucleotides from the 3'-end of exon 17 and six nucleotides from the 5'-end of intron 17 (c.1955_1958+6delCACGGTGAGC). This eliminates the 3'-splice junction of exon 17, creates an alternate splice site immediately downstream in which the processed mRNA contains a frame shift, and generates a premature stop codon predicted to truncate approximately 50% of the protein. Homozygosity for the deletion was highly associated with the severe juvenile-onset PN phenotype in both Leonberger and Saint Bernard dogs. The overall clinical picture of PN in these breeds, and the effects of sex and heterozygosity of the ARHGEF10 deletion, are less clear due to the likely presence of other forms of PN with variable ages of onset and severity of clinical signs. This is the first documented severe polyneuropathy associated with a mutation in ARHGEF10 in any species.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.