{"entity": "researcher", "timestamp": "2026-08-23T10:16:12.941Z", "family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "affiliations": ["Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Biomedical Centre, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ae1ca7083b74698be9381f90cbad008.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ae1ca7083b74698be9381f90cbad008"}}, "publications": [{"entity": "publication", "iuid": "9f1216233fb049d4bfcf825c1376fad3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9f1216233fb049d4bfcf825c1376fad3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9f1216233fb049d4bfcf825c1376fad3"}}, "title": "Epigenetic insights into GABAergic development in Dravet Syndrome iPSC and therapeutic implications.", "authors": [{"family": "Schuster", "given": "Jens", "initials": "J", "orcid": "0000-0002-4383-9880", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b027b5cce9cc488e88cbf8673f5761b2.json"}}, {"family": "Lu", "given": "Xi", "initials": "X"}, {"family": "Dang", "given": "Yonglong", "initials": "Y", "orcid": "0000-0001-9705-5507", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a828f29d1e8f40a69087ea74c89bc32c.json"}}, {"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ae1ca7083b74698be9381f90cbad008.json"}}, {"family": "Wenz", "given": "Amelie", "initials": "A"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/16529ca196d94a699959c276d3c84960.json"}}, {"family": "Chen", "given": "Xingqi", "initials": "X", "orcid": "0000-0002-5657-2839", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ffb9d3c94e54fac97be6c78586940eb.json"}}], "type": "journal article", "published": "2024-08-27", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "12", "issn-l": "2050-084X"}, "abstract": "Dravet syndrome (DS) is a devastating early-onset refractory epilepsy syndrome caused by variants in the SCN1A gene. A disturbed GABAergic interneuron function is implicated in the progression to DS but the underlying developmental and pathophysiological mechanisms remain elusive, in particularly at the chromatin level. Induced pluripotent stem cells (iPSCs) derived from DS cases and healthy donors were used to model disease-associated epigenetic abnormalities of GABAergic development. Chromatin accessibility was assessed at multiple time points (Day 0, Day 19, Day 35, and Day 65) of GABAergic differentiation. Additionally, the effects of the commonly used anti-seizure drug valproic acid (VPA) on chromatin accessibility were elucidated in GABAergic cells. The distinct dynamics in the chromatin profile of DS iPSC predicted accelerated early GABAergic development, evident at D19, and diverged further from the pattern in control iPSC with continued differentiation, indicating a disrupted GABAergic maturation. Exposure to VPA at D65 reshaped the chromatin landscape at a variable extent in different iPSC-lines and rescued the observed dysfunctional development of some DS iPSC-GABA. The comprehensive investigation on the chromatin landscape of GABAergic differentiation in DS-patient iPSC offers valuable insights into the epigenetic dysregulations associated with interneuronal dysfunction in DS. Moreover, the detailed analysis of the chromatin changes induced by VPA in iPSC-GABA holds the potential to improve the development of personalized and targeted anti-epileptic therapies.", "doi": "10.7554/eLife.92599", "pmid": "39190448", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11349296"}, {"db": "pii", "key": "92599"}, {"db": "GEO", "key": "GSE274660"}], "notes": [], "created": "2026-08-21T13:08:03.790Z", "modified": "2026-08-21T13:08:03.880Z"}, {"entity": "publication", "iuid": "e98fafc1de524cc398071c73d35d317a", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e98fafc1de524cc398071c73d35d317a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e98fafc1de524cc398071c73d35d317a"}}, "title": "A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome.", "authors": [{"family": "Delvall\u00e9e", "given": "Clarisse", "initials": "C"}, {"family": "Nicaise", "given": "Samuel", "initials": "S"}, {"family": "Antin", "given": "Manuela", "initials": "M"}, {"family": "Leuvrey", "given": "Anne-Sophie", "initials": "AS"}, {"family": "Nourisson", "given": "Elsa", "initials": "E"}, {"family": "Leitch", "given": "Carmen C", "initials": "CC"}, {"family": "Kellaris", "given": "Georgios", "initials": "G"}, {"family": "Stoetzel", "given": "Corinne", "initials": "C"}, {"family": "Geoffroy", "given": "V\u00e9ronique", "initials": "V"}, {"family": "Scheidecker", "given": "Sophie", "initials": "S"}, {"family": "Keren", "given": "Boris", "initials": "B"}, {"family": "Depienne", "given": "Christel", "initials": "C"}, {"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ae1ca7083b74698be9381f90cbad008.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}, {"family": "Deleuze", "given": "Jean-Fran\u00e7ois", "initials": "JF"}, {"family": "G\u00e9nin", "given": "Emmanuelle", "initials": "E"}, {"family": "Redon", "given": "Richard", "initials": "R"}, {"family": "Demurger", "given": "Florence", "initials": "F"}, {"family": "Devriendt", "given": "Koenraad", "initials": "K"}, {"family": "Mathieu-Dramard", "given": "Mich\u00e8le", "initials": "M"}, {"family": "Poitou-Bernert", "given": "Christine", "initials": "C"}, {"family": "Odent", "given": "Sylvie", "initials": "S"}, {"family": "Katsanis", "given": "Nicholas", "initials": "N"}, {"family": "Mandel", "given": "Jean-Louis", "initials": "JL"}, {"family": "Davis", "given": "Erica E", "initials": "EE"}, {"family": "Dollfus", "given": "H\u00e9l\u00e8ne", "initials": "H"}, {"family": "Muller", "given": "Jean", "initials": "J", "orcid": "0000-0002-7682-559X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9c09fdc928894466968b79f13f19c738.json"}}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "Clin. Genet.", "issn": "1399-0004", "volume": "99", "issue": "2", "pages": "318-324", "issn-l": "0009-9163"}, "abstract": "Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.", "doi": "10.1111/cge.13878", "pmid": "33169370", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1705693"}, {"db": "pmc", "key": "PMC8253169"}], "notes": [], "created": "2026-08-21T12:18:13.182Z", "modified": "2026-08-21T12:18:13.287Z"}, {"entity": "publication", "iuid": "6fd8ba45644e467eb0754e579905ab79", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6fd8ba45644e467eb0754e579905ab79.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6fd8ba45644e467eb0754e579905ab79"}}, "title": "Phenotypic expansion of visceral myopathy associated with ACTG2 tandem base substitution.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1ae1ca7083b74698be9381f90cbad008.json"}}, {"family": "Raykova", "given": "Doroteya", "initials": "D", "orcid": "0000-0001-6452-2199", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/310a54498df840bda10ab0cdf6c23c8a.json"}}, {"family": "Gustafson", "given": "Elisabet", "initials": "E"}, {"family": "T\u00f3thov\u00e1", "given": "Iveta", "initials": "I"}, {"family": "Ameur", "given": "Adam", "initials": "A"}, {"family": "Wanders", "given": "Alkwin", "initials": "A"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2015-12-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "volume": "23", "issue": "12", "pages": "1679-1683", "issn-l": "1018-4813"}, "abstract": "Familial visceral myopathy (FVM) is a rare heritable and heterogeneous condition due to impaired smooth muscle function. We identified a family segregating 11 individuals with a spectrum of visceral symptoms involving the small intestine, colon, biliary tract, urinary tract and uterus. Whole-exome sequencing revealed a novel heterozygous tandem base substitution c.806_807delinsAA (p.(Gly269Glu)) in ACTG2, encoding smooth muscle actin \u03b3-2, in affected family members. Variants in ACTG2 were recently identified in FVM with intestinal pseudo-obstruction as well as with the congenital megacystics-microcolon-intestinal hypoperistalsis syndrome. In our family, eight affected members presented with severe complications from the biliary and/or the urinary tracts in addition to gastrointestinal pseudo-obstructions. Furthermore, all affected mothers had a history of assisted deliveries owing to poor progress during labor and weak uterine contractions. The variable involvement of multiple smooth muscle-dependent organs in our family, including the biliary tract and the uterus, add to the phenotypic spectrum associated with ACTG2 missense variants.", "doi": "10.1038/ejhg.2015.49", "pmid": "25782675", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC4795199"}, {"db": "pii", "key": "ejhg201549"}], "notes": [], "created": "2018-12-05T11:30:30.990Z", "modified": "2026-08-21T11:41:26.435Z"}]}