Evidence map›Paper›PMID 29441694›Full record

ArticleMolecular genetics & genomic medicine2018

Presynaptic congenital myasthenic syndrome with altered synaptic vesicle homeostasis linked to compound heterozygous sequence variants in RPH3A.

Ricardo A Maselli, Jessica Vázquez, Leah Schrumpf, Juan Arredondo, Marian Lara, Jonathan B Strober, Peter Pytel, Robert L Wollmann, Michael Ferns

Open access · goldAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics & genomic medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 37% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Ricardo A MaselliDepartment of Neurology, University of California Davis, Sacramento, CA, USA.ORCID 0000-0002-0918-0760
Jessica VázquezDepartment of Neurology, University of California Davis, Sacramento, CA, USA.
Leah SchrumpfDepartment of Neurology, University of California Davis, Sacramento, CA, USA.
Juan ArredondoDepartment of Neurology, University of California Davis, Sacramento, CA, USA.
Marian LaraDepartment of Neurology, University of California Davis, Sacramento, CA, USA.
Jonathan B StroberDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.
Peter PytelDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Robert L WollmannDepartment of Pathology, University of Chicago, Chicago, IL, USA.
Michael FernsDepartment of Anesthesiology and Pain Medicine, University of California Davis, Sacramento, CA, USA.
University of California, Davis · USUniversity of Chicago · USUniversity of California Davis Medical Center · USUniversity of California, San Francisco · US

Funding

Congenital Myasthenic Syndromes: Pathogenic MechanismsR01NS049117 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MASELLI, RICARDO ANIBAL · 2010 to 2014
$1.6M
NINDS NIH HHS R01 NS049117
6 · The paper itself

Abstract

backgroundMonogenic defects of synaptic vesicle (SV) homeostasis have been implicated in many neurologic diseases, including autism, epilepsy, and movement disorders. In addition, abnormal vesicle exocytosis has been associated with several endocrine dysfunctions.

methodsWe report an 11 year old girl with learning disabilities, tremors, ataxia, transient hyperglycemia, and muscle fatigability responsive to albuterol sulfate. Failure of neuromuscular transmission was confirmed by single fiber electromyography. Electron microscopy of motor nerve terminals revealed marked reduction in SV density, double-membrane-bound sacs containing SVs, abundant endosomes, and degenerative lamellar bodies. The patient underwent whole exome sequencing (WES) and relevant sequence variants were expressed and studied in a mammalian cell line.

resultsChromosomal microarray studies and next generation sequencing (NGS) of mitochondrial DNA were unrevealing; however, NGS of genomic DNA showed two rare sequence variants in the gene encoding rabphilin 3a (RPH3A). The paternally inherited variant c.806 G>A (p.Arg269Gln) involves a substitution of a conserved residue in the linker region, while the maternally inherited variant c.1390 G>T (p.Val464Leu) involves a conserved amino acid substitution in the highly conserved C2A region. Expression studies revealed that p.Arg269Gln strongly impairs the binding of rabphilin 3a to 14-3-3, which is a proposed regulator of synaptic transmission and plasticity. In contrast, the binding of rabphilin 3a to 14-3-3 is only marginally impaired by p.Val464Leu; thus, the pathogenic role of p.Val464Leu remains unclear.

conclusionIn summary, we report a patient with a multisystem neurologic disorder and altered SV regulation attributed to defects in RPH3A, which grants further studies of this gene in human disorders of synaptic transmission.

Indexed as

Adaptor Proteins, Signal TransducingChildFemaleHeterozygoteHomeostasisHumansMicroscopy, ElectronMyasthenic Syndromes, CongenitalNerve Tissue ProteinsRabphilin-3ASynaptic TransmissionSynaptic VesiclesVesicular Transport ProteinsAdaptor Proteins, Signal TransducingNerve Tissue ProteinsRabphilin-3AVesicular Transport Proteinscongenital myasthenic syndrome (CMS)presynapticrabphilin 3aRPH3A

Identifiers

PMID29441694
PMCPMC6014458
OpenAlexW2792399758

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Registered trials

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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.