Mutations in DOCK7 in Individuals with Epileptic Encephalopathy and Cortical Blindness
Open accessAbstract
Epileptic encephalopathies are increasingly thought to be of genetic origin, although the exact etiology remains uncertain in many cases. We describe here three girls from two nonconsanguineous families affected by a clinical entity characterized by dysmorphic features, early-onset intractable epilepsy, intellectual disability, and cortical blindness. In individuals from each family, brain imaging also showed specific changes, including an abnormally marked pontobulbar sulcus and abnormal signals (T2 hyperintensities) and atrophy in the occipital lobe. Exome sequencing performed in the first family did not reveal any gene with rare homozygous variants shared by both affected siblings. It did, however, show one gene, DOCK7, with two rare heterozygous variants (c.2510delA [p.Asp837Alafs(∗)48] and c.3709C>T [p.Arg1237(∗)]) found in both affected sisters. Exome sequencing performed in the proband of the second family also showed the presence of two rare heterozygous variants (c.983C>G [p.Ser328(∗)] and c.6232G>T [p.Glu2078(∗)]) in DOCK7. Sanger sequencing confirmed that all three individuals are compound heterozygotes for these truncating mutations in DOCK7. These mutations have not been observed in public SNP databases and are predicted to abolish domains critical for DOCK7 function. DOCK7 codes for a Rac guanine nucleotide exchange factor that has been implicated in the genesis and polarization of newborn pyramidal neurons and in the morphological differentiation of GABAergic i…
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Bi-allelic null variants in DOCK7 cause epileptic encephalopathy.
“bi-allelic null variants in DOCK6 (MIM: #614,219) and DOCK7 (MIM: #615,859), members of the dedicator of cytokinesis (DOCK) family, are a cause for the Adams–Oliver syndrome (Sukalo et al. 2015) and epileptic encephalopathy (Perrault et al. 2014), respectively.”
From Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly (2024) · cites this paper as Perrault et al. 2014
Premature stop codon mutations in DOCK7 resulting in truncated protein are linked to epileptic encephalopathy and cortical blindness.
“In keeping with observations that DOCK7 is crucial for neural processes, several studies have identified pathological links between premature stop codon mutations in DOCK7 that resulted in truncated protein and epileptic encephalopathy and cortical blindness (110, 111, 112).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [112]
Cites
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,380 · see citing works
Berg, A. T., Berkovic, S. F., Brodie, M. J., Buchhalter, J., Cross, J. H., Van Emde Boas, W., Engel, J., French, J., Glauser, T. A., Mathern, G. W., et al. (2010) · Epilepsia · doi:10.1111/j.1528-1167.2010.02522.x · Cited by 4,363 · see citing works
De novo mutations in epileptic encephalopathies
Epi4K Consortium, & Epilepsy Phenome/Genome Project (2013) · Nature · doi:10.1038/nature12439 · Cited by 1,514 · see citing works
Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA functionPreprint
Isken, O., & Maquat, L. E. (2007) · Genes & Development · doi:10.1101/gad.1566807 · Cited by 584 · see citing works
GABAergic Interneurons Shape the Functional Maturation of the Cortex
Le Magueresse, C., & Monyer, H. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.011 · Cited by 425 · see citing works
GEF what? Dock180 and related proteins help Rac to polarize cells in new ways
Côté, J., & Vuori, K. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.05.001 · Cited by 322 · see citing works
The Rac Activator DOCK7 Regulates Neuronal Polarity through Local Phosphorylation of Stathmin/Op18
Watabe-Uchida, M., John, K. A., Janas, J. A., Newey, S. E., & Van Aelst, L. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.020 · Cited by 208 · see citing works
ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration
Yamauchi, J., Miyamoto, Y., Chan, J. R., & Tanoue, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200709033 · Cited by 131 · see citing works
DOCK7 interacts with TACC3 to regulate interkinetic nuclear migration and cortical neurogenesis
Yang, Y.-T., Wang, C.-L., & Van Aelst, L. (2012) · Nature Neuroscience · doi:10.1038/nn.3171 · Cited by 97 · see citing works
Regulation of Chandelier Cell Cartridge and Bouton Development via DOCK7-Mediated ErbB4 Activation
Tai, Y., Janas, J. A., Wang, C.-L., & Aelst, L. V. (2014) · Cell Reports · doi:10.1016/j.celrep.2013.12.034 · Cited by 49 · see citing works
Early myoclonic encephalopathy caused by a disruption of the neuregulin-1 receptor ErbB4
Backx, L., Ceulemans, B., Vermeesch, J. R., Devriendt, K., & Esch, H. V. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.180 · Cited by 47 · see citing works
Blasius, A. L., Brandl, K., Crozat, K., Xia, Y., Khovananth, K., Krebs, P., Smart, N. G., Zampolli, A., Ruggeri, Z. M., & Beutler, B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813208106 · Cited by 41 · see citing works
A new single gene deletion on 2q34: ERBB4 is associated with intellectual disability
Kasnauskienė, J., Čiuladaitė, Ž., Preikšaitienė, E., Utkus, A., Pečiulytė, A., & Kučinskas, V. (2013) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35911 · Cited by 31 · see citing works
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Lessons learned from additional research analyses of unsolved clinical exome cases
Eldomery, M. K., Coban-Akdemir, Z., Harel, T., Rosenfeld, J. A., Gambin, T., Stray-Pedersen, A., Küry, S., Mercier, S., Lessel, D., Denecke, J., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0412-6 · Cited by 230 · see citing works
Mnatsakanyan, R., Markoutsa, S., Walbrunn, K., Roos, A., Verhelst, S. H. L., & Zahedi, R. P. (2019) · Nature Communications · doi:10.1038/s41467-019-10182-4 · Cited by 114 · see citing works
Pagnamenta, A. T., Camps, C., Giacopuzzi, E., Taylor, J., Hashim, M., Calpena, E., Kaisaki, P. J., Hashimoto, A., Yu, J., Sanders, E., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01240-0 · Cited by 85 · see citing works
The landscape of early infantile epileptic encephalopathy in a consanguineous population
Nashabat, M., Qahtani, X. A., Makdob, S. A., Altwaijri, W. A., Baarmah, D., Hundallah, K. J., Alhashem, A. M., Tala, S. A., Maddirevula, S., Alkuraya, F. S., et al. (2019) · Seizure · doi:10.1016/j.seizure.2019.04.018 · Cited by 65 · see citing works
Shedding Light on Chandelier Cell Development, Connectivity, and Contribution to Neural Disorders
Gallo, N. B., Paul, A., & Aelst, L. V. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.003 · Cited by 54 · see citing works
Labonne, J. D. J., Shen, Y., Kong, I., Diamond, M. P., Layman, L. C., & Kim, H. (2016) · Molecular Cytogenetics · doi:10.1186/s13039-016-0234-z · Cited by 54 · see citing works
The DOCK protein family in vascular development and disease
Benson, C. E., & Southgate, L. (2021) · Angiogenesis · doi:10.1007/s10456-021-09768-8 · Cited by 46 · see citing works
Bai, Y., Xiang, X., Liang, C., & Shi, L. (2015) · BioMed Research International · doi:10.1155/2015/632450 · Cited by 40 · see citing works
Novel Genes of Early-Onset Epileptic Encephalopathies: From Genotype to Phenotypes
Mastrangelo, M. (2015) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2015.04.001 · Cited by 35 · see citing works
de Curtis, I. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00307 · Cited by 31 · see citing works
Modeling epileptic spasms during infancy: Are we heading for the treatment yet?
Velı́šek, L., & Velı́šková, J. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107578 · Cited by 31 · see citing works
Interneuron odyssey: molecular mechanisms of tangential migration
Toudji, I., Toumi, A., Chamberland, É., & Rossignol, E. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1256455 · Cited by 29 · see citing works
Self-citationHelbig, K. L., Mroske, C., Moorthy, D., Sajan, S. A., & Velinov, M. T. (2017) · Clinical Genetics · doi:10.1111/cge.12995 · Cited by 23 · see citing works
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Mallela, A. N., Deng, H., Brisbin, A. K., Bush, A., & Goldschmidt, E. (2020) · Scientific Reports · doi:10.1038/s41598-020-71535-4 · Cited by 23 · see citing works
Guo, T., Yin, R., Lin, W., Wang, W., Huang, F., & Pan, S. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12713 · Cited by 22 · see citing works
Thompson, A. P., Bitsina, C., Gray, J. L., von Delft, F., & Brennan, P. E. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100521 · Cited by 21 · see citing works
Sobczak, M., Chumak, V., Pomorski, P., Wojtera, E., Majewski, Ł., Nowak, J., Yamauchi, J., & Rędowicz, M. J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.03.020 · Cited by 20 · see citing works
Rahman, M., & Fatema, K. (2021) · Journal of Epilepsy Research · doi:10.14581/jer.21004 · Cited by 18 · see citing works
Quantitative interactome proteomics identifies a proteostasis network for GABAA receptors
Wang, Y., Di, X.-J., & Mu, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102423 · Cited by 19 · see citing works
Epilepsy genetics: The ongoing revolution
Lesca, G., & Depienne, C. (2015) · Revue Neurologique · doi:10.1016/j.neurol.2015.01.569 · Cited by 18 · see citing works
DOCK7 protects against replication stress by promoting RPA stability on chromatin
Gao, M., Guo, G., Huang, J., Hou, X., Ham, H., Kim, W., Zhao, F., Tu, X., Zhou, Q., Zhang, C., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab134 · Cited by 19 · see citing works
Iwata‐Otsubo, A., Ritter, A. L., Weckselbatt, B., Ryan, N. R., Burgess, D., Conlin, L. K., & Izumi, K. (2017) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.38517 · Cited by 17 · see citing works
Gonsales, M. C., Montenegro, M. A., Soler, C. V., Coan, A. C., Guerreiro, M. M., & Lopes‐Cendes, Í. (2015) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x20150122 · Cited by 17 · see citing works
Andrews, T. S., Meader, S., Silfhout, A. V., Taylor, A., Steinberg, J., Hehir‐Kwa, J. Y., Pfundt, R., de Leeuw, N., Vries, B. B. A. D., & Webber, C. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1005012 · Cited by 14 · see citing works
Genetic screening and diagnosis in epilepsy?
Sisodiya, S. M. (2015) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000180 · Cited by 15 · see citing works
Le, P. T., Bishop, K. A., Maridas, D. E., Motyl, K. J., Brooks, D. J., Nagano, K., Baron, R., Bouxsein, M., & Rosen, C. J. (2017) · Bone · doi:10.1016/j.bone.2017.08.006 · Cited by 14 · see citing works
Emond, M. R., Biswas, S., Morrow, M. L., & Jontes, J. D. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.09.033 · Cited by 10 · see citing works
Unravelling the genetic architecture of autosomal recessive epilepsy in the genomic era
Calhoun, J. D., & Carvill, G. L. (2018) · Journal of Neurogenetics · doi:10.1080/01677063.2018.1513509 · Cited by 10 · see citing works
Magalhães, P. H. M., de Moraes, H. T., Athié, M. C. P., Secolin, R., & Lopes‐Cendes, Í. (2019) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2019.07.029 · Cited by 10 · see citing works
Novel DOCK7 mutations in a Chinese patient with early infantile epileptic encephalopathy 23
Bai, B., Guo, Y.-R., Zhang, Y.-H., Jin, C.-C., Zhang, J.-M., Chen, H., & Zhu, B.-S. (2019) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000100 · Cited by 9 · see citing works
A novel truncating mutation of DOCK7 gene with an early-onset non-encephalopathic epilepsy
Turkdogan, D., Turkyilmaz, A., Gormez, Z., Sager, G., & Ekinci, G. (2019) · Seizure · doi:10.1016/j.seizure.2019.01.010 · Cited by 8 · see citing works
Li, L., Liu, Z., Yang, H., Li, Y., Zeng, Q., Chen, L., Liu, Y., Chen, Y., Zhu, F., Cao, D., et al. (2022) · Seizure · doi:10.1016/j.seizure.2022.09.004 · Cited by 8 · see citing works
Heterozygous loss-of-function variants in DOCK4 cause neurodevelopmental delay and microcephaly
Herbst, C., Bothe, V., Wegler, M., Axer-Schaefer, S., Audebert-Bellanger, S., Gecz, J., Cogne, B., Feldman, H. B., Horn, A. H. C., Hurst, A. C. E., et al. (2024) · Human Genetics · doi:10.1007/s00439-024-02655-4 · Cited by 7 · see citing works
“…(MIM: #614,219) and DOCK7 (MIM: #615,859), members of the dedicator of cytokinesis (DOCK) family, are Extended author information available on the last page of the article a cause for the Adams–Oliver syndrome (Sukalo et al. 2015) and epileptic encephalopathy (Perrault et al. 2014), respectively.”
BackgroundHaberlandt, E., Valovka, T., Janjic, T., Müller, T., Blatsios, G., Karall, D., & Janecke, A. (2021) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1607 · Cited by 7 · see citing works
Pfiffner, F. K., Koller, S., Ménétrey, A., Graf, U., Bähr, L., Maspoli, A., Hackenberg, A., Kottke, R., Gerth‐Kahlert, C., & Berger, W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137382 · Cited by 4 · see citing works
Carrascosa-Romero, M. C., & de Cabo, C. (2016) · InTech eBooks · doi:10.5772/64458 · Cited by 2 · see citing works
Oey, N. E., Zhou, L., Chan, C. H. S., VanDongen, A. M. J., & Tan, E. K. (2023) · Biomedicines · doi:10.3390/biomedicines11020486 · Cited by 2 · see citing works
Ghate, P. S., Vacharasin, J. M., Ward, J. A., Nowling, D., Kay, V. E., Cowen, M. H., Lawlor, M.-K., McCord, M. M., Xu, H., Carmona, E., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106215 · Cited by 2 · see citing works
Disorders of sexual development associated with sex chromosomes: an update
Santamaría-Durán, N., Suárez‐Obando, F., & Rojas, A. P. (2022) · Revista Mexicana de Urología · doi:10.48193/revistamexicanadeurologa.v82i4.910 · Cited by 1 · see citing works
Guzmán-Jiménez, D. E., Flores-Ramírez, E. L., & Velasco-Monroy, A. L. (2019) · Revista Médica Del Hospital General De México · doi:10.24875/hgmx.m19000001 · Cited by 1 · see citing works
Microglia and Fn14 regulate transcription and chromatin accessibility in developing neuronsPreprint
Ferro, A., Vrudhula, U., Auguste, Y. S. S., & Cheadle, L. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.16.456505 · Cited by 1 · see citing works
DOCK7 regulates WNT signaling and NMJ clustering in normal and DMD musclePreprint
English, K. G., Rorrer, S. N., Karuppasamy, M., Becker, K. A., Crossman, D. K., Lopez, M. A., Thalacker‐Mercer, A. E., & Alexander, M. S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.23.696254 · Cited by 1 · see citing works
Deletion of Dock7 Exons 3 and 4 Results in Reduced Trabecular Bone MicroarchitecturePreprint
Lizotte, T., Lajoie, C. R., Porter, S. R., Lang, S., Vesper, F., Brooks, D. J., Gartner, C. A., Alexander, M. S., Vary, C., Bouxsein, M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.31.696872 · Cited by 1 · see citing works
Kapoor, D., Anand, A., Siddiqui, S., & Sharma, S. (2021) · Clinical Dysmorphology · doi:10.1097/mcd.0000000000000393
Özsoy, Ö., Çinleti, T., Zeybek, S., Soydemir, D., Uzan, G. S., Günay, Ç., Kurul, S. H., & Yiş, U. (2023) · Neurology Asia · doi:10.54029/2023exu
Genetic Diversity in Early Infantile Epileptic Encephalopathy: A Three-Year Cohort Study
Torbati, P. N., Salehirozveh, M., Toosi, M. B., Ahangari, N., Doosti, M., Ashrafzadeh, F., Akhondian, J., Hashemi, N., Safi, M., Mirzadeh, H. S., et al. (2026) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2025.12.015
Ferland, R. J., Lizotte, T., & Becker, K. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.22.720243
Pai, A., Dcunha, L., Gopalakrishnan, A. P., Ummar, S., Rajeev, A. C., & Raju, R. (2026) · OMICS A Journal of Integrative Biology · doi:10.1177/15578100261470540
- Authors
- Perrault, I., Hamdan, F. F., Rio, M., Capo-Chichi, J.-M., Boddaert, N., Décarie, J.-C., Maranda, B., Nabbout, R., Sylvain, M., Lortie, A., Roux, P. P., Rossignol, E., Gérard, X., Barcia, G., Berquin, P., Munnich, A., Rouleau, G. A., Kaplan, J., Rozet, J.-M., & Michaud, J. L.
- Affiliations
- Inserm (FR)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Hôpital Necker-Enfants Malades (FR)
- Centre Hospitalier Universitaire de Sherbrooke (CA)
- Centre hospitalier universitaire de Québec (CA)
- Institute for Research in Immunology and Cancer (CA)
- Centre Hospitalier Universitaire Amiens-Picardie (FR)
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- Rozet, Jean-Michel
- Michaud, Jacques L.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 94
- Issue
- 6
- Pages
- 891-897
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC4121477
- OpenAlex
- W2073078550
- Cited by
- 50
- References
- 13
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 1
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- DOCK7, epileptic encephalopathy, cortical blindness, compound heterozygosity, truncating mutations, drug-resistant epilepsy, intellectual disability, dysmorphic features, exome sequencing, rare variants
- MeSH terms
- Child, Child, Preschool, Epilepsy, Epilepsies, Myoclonic, Female, Genes, Recessive, Heterozygote, Homozygote, Humans, Infant, Male, Intellectual Disability, Mutation, Pedigree, Phenotype, Spasms, Infantile, Sequence Analysis, DNA, Blindness, Cortical, Polymorphism, Single Nucleotide, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins, Exome
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