ArticleNature communications2019
Comprehensive analysis of coding variants highlights genetic complexity in developmental and epileptic encephalopathy.
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Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42citing papers in PubMed
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Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
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- The molecular basis of KCNH1-related epileptic encephalopathy and the challenge of developing targeted therapeutics.Brain : a journal of neurology · 2026Review
- Genomics and epilepsy: Opportunities to improve understanding and management.Developmental medicine and child neurology · 2026Review
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- Identification of three novel GNAO1 variants in a Chinese cohort with GNAO1 encephalopathy: expanding the clinical and genetic spectrum.Orphanet journal of rare diseases · 2025Article
- Monogenic Epilepsies in Adult Epilepsy Clinics and Gene-Driven Approaches to Treatment.Current neurology and neuroscience reports · 2025Review
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- Association between maternal usage of volatile organic compounds and West syndrome, the Japan Environment and Children's study.Scientific reports · 2024Article
- Genetic Variant Analyses Identify Novel Candidate Autism Risk Genes from a Highly Consanguineous Cohort of 104 Families from Oman.International journal of molecular sciences · 2024Article
- Clinical features and underlying etiology of children with Lennox-Gastaut syndrome.Journal of neurology · 2024Article
- Clinical features and genetic analysis of developmental and epileptic encephalopathy caused by biallelic variants ofHeliyon · 2024Article
- High-multiplex single-cell imaging analysis reveals tumor immune contexture associated with clinical outcomes after CAR T cell therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
65 authors at 20 institutions in 1 country.
Atsushi TakataDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. atakata@yokohama-cu.ac.jp.
Mitsuko NakashimaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.ORCID http://orcid.org/0000-0001-7941-1774
Hirotomo SaitsuDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.ORCID http://orcid.org/0000-0003-0723-0960
Takeshi MizuguchiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Satomi MitsuhashiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Yukitoshi TakahashiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Nobuhiko OkamotoDepartment of Medical Genetics, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.
Hitoshi OsakaDepartment of Pediatrics, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Japan.ORCID http://orcid.org/0000-0002-1320-1165
Kazuyuki NakamuraDepartment of Pediatrics, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.
Jun TohyamaDepartment of Child Neurology, NHO Nishiniigata Chuo Hospital, 1-14-1 Masago, Nishi-ku, Niigata, 950-2085, Japan.
Kazuhiro HaginoyaDepartment of Pediatric Neurology, Miyagi Children's Hospital, 4-3-17 Ochiai, Aoba-ku, Sendai, 989-3126, Japan.
Saoko TakeshitaDepartment of Pediatrics, Yokohama City University Medical Center, 4-57 Urafunecho, Minami-ku, Yokohama, 232-0024, Japan.
Ichiro KukiDepartment of Pediatric Neurology, Osaka City General Hospital, 2-13-22 Miyakojimahondori, Miyakojima-ku, Osaka, 534-0021, Japan.
Tohru OkanishiDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu, 430-8558, Japan.
Tomohide GotoDivision of Neurology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama, 232-8555, Japan.
Masayuki SasakiDepartment of Child Neurology, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, 187-8551, Japan.
Yasunari SakaiDepartment of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Noriko MiyakeDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Satoko MiyatakeDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Naomi TsuchidaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Kazuhiro IwamaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Gaku MinaseDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Futoshi SekiguchiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Atsushi FujitaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Eri ImagawaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Eriko KoshimizuDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Yuri UchiyamaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Kohei HamanakaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Chihiro OhbaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Toshiyuki ItaiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Hiromi AoiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Ken SaidaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Tomohiro SakaguchiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Kouhei DenDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.ORCID http://orcid.org/0000-0001-6741-9672
Rina TakahashiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Hiroko IkedaNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Tokito YamaguchiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Kazuki TsukamotoNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Shinsaku YoshitomiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Taikan OboshiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Katsumi ImaiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka, 420-8688, Japan.
Tomokazu KimizuDepartment of Pediatric Neurology, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.
Yu KobayashiDepartment of Child Neurology, NHO Nishiniigata Chuo Hospital, 1-14-1 Masago, Nishi-ku, Niigata, 950-2085, Japan.
Masaya KubotaDivision of Neurology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Hirofumi KashiiDivision of Neurology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Shimpei BabaDepartment of Child Neurology, Comprehensive Epilepsy Center, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu, 430-8558, Japan.
Mizue IaiDivision of Neurology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama, 232-8555, Japan.
Ryutaro KiraDepartment of Pediatric Neurology, Fukuoka Children's Hospital, 5-1-1 Kashiiteriha, Higashi-ku, Fukuoka, 813-0017, Japan.
Munetsugu HaraDepartment of Pediatrics and Child Health, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.
Masayasu OhtaDepartment of Neuropediatrics, Aiseikai Memorial Ibaraki Welfare Medical Center, 1872-1 Motoyoshida-cho, Mito, 310-0836, Japan.
Yohane MiyataDepartment of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu, 183-0042, Japan.
Rie MiyataDepartment of Pediatrics, Tokyo-kita Medical Center, 4-17-56 Akabanedai, Kita-ku, Tokyo, 115-0053, Japan.
Jun-Ichi TakanashiDepartment of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owadashinden, Yachiyo, 276-8524, Japan.
Jun MatsuiDepartment of Pediatrics, Shiga University of Medical Science, Setatsukinowacho, Otsu, 520-2192, Japan.
Kenji YokochiDepartment of Pediatric Neurology, Seirei-Mikatahara General Hospital, 3453 Mikatahara-cho, Kita-ku, Hamamatsu, 431-1304, Japan.
Masayuki ShimonoDepartment of Pediatrics, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Masano AmamotoKutakyushu Municipal Yahata Hospital Pediatric Emergency Center, 4-18-1 Nishihonmachi, Yahatahigashi-ku, Kutakyushu, 805-8534, Japan.
Rumiko TakayamaHokkaido Medical Center for Child Health and Rehabilitation, 1-240-6 Kanayama 1-jo, Teine-ku, Sapporo, 006-0041, Japan.
Shinichi HirabayashiDivision of Neurology, Nagano Children's Hospital, 3100 Toyoshina, Azumino, 399-8288, Japan.
Kaori AibaDepartment of Pediatrics, Toyohashi Municipal Hospital, 50 Aza Hachiken Nishi, Aotake-Cho, Toyohashi, 441-8570, Japan.
Hiroshi MatsumotoDepartment of Pediatrics, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.
Shin NabatameDepartment of Pediatrics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Japan.ORCID http://orcid.org/0000-0001-8453-2028
Takashi ShiiharaDepartment of Neurology, Gunma Children's Medical Center, 779 Shimohakoda, Hokkitsu-machi, Shibukawa, 377-8577, Japan.
Mitsuhiro KatoDepartment of Pediatrics, Yamagata University Faculty of Medicine, 2-2-2 Iida-nishi, Yamagata, 990-9585, Japan.ORCID http://orcid.org/0000-0003-1485-8553
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. naomat@yokohama-cu.ac.jp.ORCID http://orcid.org/0000-0001-9846-6500
Yokohama City University · JPNational Epilepsy Center · JPHamamatsu University School of Medicine · JPKanagawa Children's Medical Center · JPNational Center For Child Health and Development · JPNishi Niigata Chuo National Hospital · JPOsaka Women's and Children's Hospital · JPSeirei Hamamatsu General Hospital · JPYamagata University · JPFukuoka Children's Hospital and Medical Center for Infectious Diseases · JPGunma Children's Medical Center · JPJichi Medical University · JPKitakyushu City Hospital Organization · JPKurume University · JPKyushu University · JPMito Saiseikai General Hospital · JPMiyagi Children's Hospital · JPNagano Children's Hospital · JPNational Center of Neurology and Psychiatry · JPNational Defense Medical College · JP
Funding
Japan Agency for Medical Research and Development (AMED) JP18ek0109280MEXT | Japan Society for the Promotion of Science (JSPS) JP17H01539
Abstract
Although there are many known Mendelian genes linked to epileptic or developmental and epileptic encephalopathy (EE/DEE), its genetic architecture is not fully explained. Here, we address this incompleteness by analyzing exomes of 743 EE/DEE cases and 2366 controls. We observe that damaging ultra-rare variants (dURVs) unique to an individual are significantly overrepresented in EE/DEE, both in known EE/DEE genes and the other non-EE/DEE genes. Importantly, enrichment of dURVs in non-EE/DEE genes is significant, even in the subset of cases with diagnostic dURVs (P = 0.000215), suggesting oligogenic contribution of non-EE/DEE gene dURVs. Gene-based analysis identifies exome-wide significant (P = 2.04 × 10
Indexed as
Genetic VariationAdaptor Proteins, Vesicular TransportAsian PeopleCase-Control StudiesDNA (Cytosine-5-)-MethyltransferasesEpilepsies, MyoclonicExome SequencingGuanine Nucleotide Exchange FactorsHumansInfantJapanLennox Gastaut SyndromeLogistic ModelsMutationNeurofibromin 1Polymorphism, Single NucleotideAdaptor Proteins, Vesicular TransportAP5B1 protein, humanARFGEF1 protein, humanDNA (Cytosine-5-)-MethyltransferasesDNMT3L protein, humanGuanine Nucleotide Exchange FactorsNeurofibromin 1NF1 protein, humanTRPM5 protein, humanTRPM Cation Channels
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