{"entity": "researcher", "timestamp": "2026-09-23T18:38:59.197Z", "family": "Ygberg", "given": "Sofia", "initials": "S", "orcid": "0000-0002-3854-2716", "affiliations": ["Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.", "Centre for Inherited Metabolic Diseases, Karolinska University Hospital, 17176 Stockholm, Sweden.", "Department of Child Neurology, Karolinska University Hospital, 17176 Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b032359f6bf48be84cbb595142d9382.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b032359f6bf48be84cbb595142d9382"}}, "publications": [{"entity": "publication", "iuid": "9dae0bf5779946f385b54f2fd79aff0e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/9dae0bf5779946f385b54f2fd79aff0e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/9dae0bf5779946f385b54f2fd79aff0e"}}, "title": "Novel Synonymous and Deep Intronic Variants Causing Primary and Secondary Pyruvate Dehydrogenase Complex Deficiency.", "authors": [{"family": "Bruhn", "given": "Helene", "initials": "H", "orcid": "0009-0007-4449-5382", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8f53e5d30e740bfa10ff7b714c52627.json"}}, {"family": "Naess", "given": "Karin", "initials": "K", "orcid": "0000-0003-4310-7927", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8a2a99562d874e77a23e871a91335d89.json"}}, {"family": "Ygberg", "given": "Sofia", "initials": "S", "orcid": "0000-0002-3854-2716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b032359f6bf48be84cbb595142d9382.json"}}, {"family": "Pe\u00f1a-P\u00e9rez", "given": "Luc\u00eda", "initials": "L", "orcid": "0000-0002-5044-7754", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/588586bc4a6b4b9ab13e10d0b83cfe53.json"}}, {"family": "Lesko", "given": "Nicole", "initials": "N", "orcid": "0000-0001-8770-1878", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9797b7e046474000903bc5d5046abd9e.json"}}, {"family": "Wibom", "given": "Rolf", "initials": "R", "orcid": "0000-0001-6721-4642", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/54b1320b61854e40a99e9e2d22d2721f.json"}}, {"family": "Freyer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-0418-1673", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fba742fee9324f4ba469cc84a6bfd9c6.json"}}, {"family": "Stranneheim", "given": "Henrik", "initials": "H", "orcid": "0009-0009-1335-8021", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0611f45194a44f15a668914498bd262c.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9ba593bf3e472fa7d157cd697c7427.json"}}, {"family": "Wredenberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-2500-6121", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1bd991602b184ab48a4dca93b7901466.json"}}], "type": "journal article", "published": "2024-03-25", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "2024", "pages": "1611838", "issn-l": "1059-7794"}, "abstract": "Pyruvate dehydrogenase complex deficiency (PDCD) is a defect of aerobic carbohydrate metabolism that causes neurological disorders with varying degrees of severity. We report the clinical, biochemical, and molecular findings in patients with primary and secondary PDCD caused by novel atypical genetic variants. Whole-genome sequencing (WGS) identified the synonymous variants c.447A>G, p.(Lys149=) and c.570C>T, p.(Cys190=) in pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), the deep intronic variants c.1023+2267G>A and c.1023+2302A>G in pyruvate dehydrogenase complex component X (PDHX), and c.185+15054G>A in thiamine pyrophosphokinase (TPK1). Analysis by Sanger and RNA sequencing of cDNA from patient blood and/or cultured fibroblasts showed that the synonymous variants in PDHA1 lead to aberrant splicing and skipping of exons 5 and 5-6 in one of the patients and transcripts lacking exon 6 in the other. The deep intronic variants in PDHX and TPK1 lead to insertion of intronic sequence in the corresponding transcripts. The splice defects in PDHA1 were more pronounced in cultured fibroblasts than in blood. Our findings expand the spectrum of pathogenic variants causing PDCD and highlight the importance of atypical variants leading to aberrant splicing. The severity of the splice defects and resulting biochemical dysfunction varied between tissues, stressing the importance of performing biochemical and transcript analysis in affected tissues. The two males with hemizygous synonymous PDHA1 variants have a mild phenotype and higher PDH enzyme activity than expected, which is consistent with aberrant but leaky splicing with a proportion of the transcripts remaining correctly spliced.", "doi": "10.1155/2024/1611838", "pmid": "40225937", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11919216"}], "notes": [], "created": "2026-09-23T12:29:12.663Z", "modified": "2026-09-23T12:29:12.930Z"}, {"entity": "publication", "iuid": "026e176cc2744047a1ae797684e42264", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/026e176cc2744047a1ae797684e42264.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/026e176cc2744047a1ae797684e42264"}}, "title": "A missense mutation converts the Na+,K+-ATPase into an ion channel and causes therapy-resistant epilepsy.", "authors": [{"family": "Ygberg", "given": "Sofia", "initials": "S", "orcid": "0000-0002-3854-2716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b032359f6bf48be84cbb595142d9382.json"}}, {"family": "Akkuratov", "given": "Evgeny E", "initials": "EE", "orcid": "0000-0002-2552-9512", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abd9e4662bb543eebb0451af868bc319.json"}}, {"family": "Howard", "given": "Rebecca J", "initials": "RJ", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc9bc4b87d0f43b9a0528e936921e5ae.json"}}, {"family": "Jans", "given": "Daniel C", "initials": "DC", "orcid": "0000-0002-6356-9742", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ff40f8719c944e6b0ff27ded3b05a27.json"}}, {"family": "Mahato", "given": "Dhani R", "initials": "DR"}, {"family": "Katz", "given": "Adriana", "initials": "A"}, {"family": "Kinoshita", "given": "Paula F", "initials": "PF"}, {"family": "Portal", "given": "Benjamin", "initials": "B"}, {"family": "Nennesmo", "given": "Inger", "initials": "I"}, {"family": "Lindskog", "given": "Maria", "initials": "M", "orcid": "0000-0001-9484-1983", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/de1f718eadcd41b7b3d5834bf34886b1.json"}}, {"family": "Karlish", "given": "Steven J D", "initials": "SJD"}, {"family": "Andersson", "given": "Magnus", "initials": "M"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04321d9fb805493db538489927a42c8f.json"}}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "case reports", "published": "2021-12-00", "journal": {"title": "J Biol Chem", "issn": "1083-351X", "volume": "297", "issue": "6", "pages": "101355", "issn-l": "0021-9258"}, "abstract": "The ion pump Na+,K+-ATPase is a critical determinant of neuronal excitability; however, its role in the etiology of diseases of the central nervous system (CNS) is largely unknown. We describe here the molecular phenotype of a Trp931Arg mutation of the Na+,K+-ATPase catalytic \u03b11 subunit in an infant diagnosed with therapy-resistant lethal epilepsy. In addition to the pathological CNS phenotype, we also detected renal wasting of Mg2+. We found that membrane expression of the mutant \u03b11 protein was low, and ion pumping activity was lost. Arginine insertion into membrane proteins can generate water-filled pores in the plasma membrane, and our molecular dynamic (MD) simulations of the principle states of Na+,K+-ATPase transport demonstrated massive water inflow into mutant \u03b11 and destabilization of the ion-binding sites. MD simulations also indicated that a water pathway was created between the mutant arginine residue and the cytoplasm, and analysis of oocytes expressing mutant \u03b11 detected a nonspecific cation current. Finally, neurons expressing mutant \u03b11 were observed to be depolarized compared with neurons expressing wild-type protein, compatible with a lowered threshold for epileptic seizures. The results imply that Na+,K+-ATPase should be considered a neuronal locus minoris resistentia in diseases associated with epilepsy and with loss of plasma membrane integrity.", "doi": "10.1016/j.jbc.2021.101355", "pmid": "34717959", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8637647"}, {"db": "pii", "key": "S0021-9258(21)01161-3"}], "notes": [], "created": "2026-09-23T10:14:51.669Z", "modified": "2026-09-23T14:51:35.637Z"}, {"entity": "publication", "iuid": "be6db8cdc6054b1b8b4b6ac5ed169c13", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/be6db8cdc6054b1b8b4b6ac5ed169c13.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/be6db8cdc6054b1b8b4b6ac5ed169c13"}}, "title": "Defective membrane insertion of mutant Na,K\u2010ATPase, a cause of fatal epilepsy", "authors": [{"family": "Howard", "given": "Rebecca", "initials": "R", "orcid": "0000-0003-2049-3378", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5ce04593b5b24aaa8978fda1447dd0bf.json"}}, {"family": "Ygberg", "given": "Sofia", "initials": "S", "orcid": "0000-0002-3854-2716", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0b032359f6bf48be84cbb595142d9382.json"}}, {"family": "Andersson", "given": "Magnus", "initials": "M"}, {"family": "Akkuratov", "given": "Evgeny", "initials": "E", "orcid": "0000-0002-2552-9512", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/abd9e4662bb543eebb0451af868bc319.json"}}, {"family": "Jans", "given": "Daniel", "initials": "D", "orcid": "0000-0002-6356-9742", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9ff40f8719c944e6b0ff27ded3b05a27.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/04321d9fb805493db538489927a42c8f.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "journal-article", "published": "2020-04-00", "journal": {"title": "The FASEB Journal", "issn": "0892-6638", "volume": "34", "issue": "S1", "pages": "1-1", "issn-l": "0892-6638"}, "abstract": null, "doi": "10.1096/fasebj.2020.34.s1.05054", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:51:52.175Z", "modified": "2026-09-23T15:02:52.978Z"}]}