Variants in CPLX1 in two families with autosomal-recessive severe infantile myoclonic epilepsy and ID
Open accessAbstract
For a large number of individuals with intellectual disability (ID), the molecular basis of the disorder is still unknown. However, whole-exome sequencing (WES) is providing more and more insights into the genetic landscape of ID. In the present study, we performed trio-based WES in 311 patients with unsolved ID and additional clinical features, and identified homozygous CPLX1 variants in three patients with ID from two unrelated families. All displayed marked developmental delay and migrating myoclonic epilepsy, and one showed a cerebellar cleft in addition. The encoded protein, complexin 1, is crucially involved in neuronal synaptic regulation, and homozygous Cplx1 knockout mice have the earliest known onset of ataxia seen in a mouse model. Recently, a homozygous truncating variant in CPLX1 was suggested to be causative for migrating epilepsy and structural brain abnormalities. ID was not reported although it cannot be completely ruled out. However, the currently limited knowledge on CPLX1 suggests that loss of complexin 1 function may lead to a complex but variable clinical phenotype, and our findings encourage further investigations of CPLX1 in patients with ID, developmental delay and myoclonic epilepsy to unravel the phenotypic spectrum of carriers of CPLX1 variants.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The genetic landscape of the epileptic encephalopathies of infancy and childhood
McTague, A., Howell, K. B., Cross, J. H., Kurian, M. A., & Scheffer, I. E. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00250-1 · Cited by 605 · see citing works
Karaca, E., Harel, T., Pehli̇van, D., Jhangiani, S. N., Gambin, T., Coban‐Akdemir, Z., Gonzaga-Jauregui, C. G., Erdin, S., Bayram, Y., Campbell, I. M., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.09.048 · Cited by 315 · see citing works
Should I stop or should I go? The role of complexin in neurotransmitter release
Trimbuch, T., & Rosenmund, C. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2015.16 · Cited by 163 · see citing works
Kuechler, A., Willemsen, M. H., Albrecht, B., Bacino, C. A., Bartholomew, D. W., van Bokhoven, H., van den Boogaard, M. J. H., Bramswig, N. C., Büttner, C., Cremer, K., et al. (2014) · Human Genetics · doi:10.1007/s00439-014-1498-1 · Cited by 124 · see citing works
Self-citationMembrane curvature sensing by the C-terminal domain of complexin
Snead, D., Wragg, R. T., Dittman, J. S., & Eliezer, D. (2014) · Nature Communications · doi:10.1038/ncomms5955 · Cited by 84 · see citing works
Glynn, D., Drew, C. J. G., Reim, K., Brose, N., & Morton, A. J. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi239 · Cited by 79 · see citing works
Chang, S., Reim, K., Pedersen, M., Neher, E., Brose, N., & Taschenberger, H. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4841-14.2015 · Cited by 66 · see citing works
Drew, C. J. G., Kyd, R. J., & Morton, A. J. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm181 · Cited by 51 · see citing works
Altered Complexin Expression in Psychiatric and Neurological Disorders: Cause or Consequence?
Brose, N. (2008) · Molecules and Cells · doi:10.1016/s1016-8478(23)17545-5 · Cited by 47 · see citing works
Early motor development is abnormal in complexin 1 knockout mice
Glynn, D., Sizemore, R. J., & Morton, A. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.10.011 · Cited by 38 · see citing works
Cerebellar disruptions and neurodevelopmental disabilities
Bosemani, T., & Poretti, A. (2016) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2016.04.014 · Cited by 27 · see citing works
Tensor-Based Morphometry and Stereology Reveal Brain Pathology in the Complexin1 Knockout Mouse
Kielar, C., Sawiak, S. J., Negredo, P. N., Tse, D. H. Y., & Morton, A. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032636 · Cited by 23 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
SNAREopathies: Diversity in Mechanisms and Symptoms
Verhage, M., & Sørensen, J. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.05.036 · Cited by 121 · see citing works
Developmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 128 · see citing works
De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy
Klöckner, C., Sticht, H., Zacher, P., Popp, B., Babcock, H. E., Bakker, D. P., Barwick, K., Bonfert, M. V., Bönnemann, C. G., Brilstra, E. H., et al. (2021) · Genetics in Medicine · doi:10.1038/s41436-020-01020-w · Cited by 47 · see citing works
Self-citation
- Authors
- Redler, S., Strom, T. M., Wieland, T., Cremer, K., Engels, H., Distelmaier, F., Schaper, J., Küchler, A., Lemke, J. R., Jeschke, S., Schreyer, N., Sticht, H., Koch, M., Lüdecke, H.-J., & Wieczorek, D.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Helmholtz Munich (DE)
- University of Bonn (DE)
- University of Duisburg-Essen (DE)
- Leipzig University (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Witten/Herdecke University (DE)
- Corresponding author
- Redler, Silke
- ORCID
- Venue
- European Journal of Human Genetics
- Published
- 2017-04-19
- Volume
- 25
- Issue
- 7
- Pages
- 889-893
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC5520065
- OpenAlex
- W2606727528
- Cited by
- 38
- References
- 12
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 2 · 2018: 3 · 2017: 1
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- complexin-1, intellectual disability, autosomal recessive inheritance, homozygous variant, developmental delay, synaptic regulation, phenotypic spectrum
- MeSH terms
- Child, Child, Preschool, Epilepsies, Myoclonic, Female, Genes, Recessive, Humans, Male, Intellectual Disability, Mutation, Nerve Tissue Proteins, Phenotype, Syndrome, Adaptor Proteins, Vesicular Transport
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
