{"entity": "researcher", "timestamp": "2026-09-23T18:49:15.013Z", "family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "affiliations": ["Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.", "Centre for Inherited Metabolic Diseases, Karolinska University Hospital, Stockholm, Sweden.", "Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9ba593bf3e472fa7d157cd697c7427.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9ba593bf3e472fa7d157cd697c7427"}}, "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": "a0e03b765e384ea89f57c34fd48a30b4", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a0e03b765e384ea89f57c34fd48a30b4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a0e03b765e384ea89f57c34fd48a30b4"}}, "title": "PatientMatcher: A customizable Python-based open-source tool for matching undiagnosed rare disease patients via the Matchmaker Exchange network.", "authors": [{"family": "Rasi", "given": "Chiara", "initials": "C", "orcid": "0000-0002-7001-3988", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6dde34e53e6d4b6a85914ad12cb6299c.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/49e071495ddf43e5b570dfb22c1fec06.json"}}, {"family": "Magnusson", "given": "M\u00e5ns", "initials": "M", "orcid": "0000-0002-0001-1047", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/42a30865d19844979f57c37b7403f93a.json"}}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/be7aa52cf290424f8f544a0034a1543a.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9ba593bf3e472fa7d157cd697c7427.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3d28fb4cc61f4033b2ac525fed3d6b94.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a4f538e838c483eb968174f2df89165.json"}}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2022-06-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "43", "issue": "6", "pages": "708-716", "issn-l": "1059-7794"}, "abstract": "The amount of data available from genomic medicine has revolutionized the approach to identify the determinants underlying many rare diseases. The task of confirming a genotype-phenotype causality for a patient affected with a rare genetic disease is often challenging. In this context, the establishment of the Matchmaker Exchange (MME) network has assumed a pivotal role in bridging heterogeneous patient information stored on different medical and research servers. MME has made it possible to solve rare disease cases by \"matching\" the genotypic and phenotypic characteristics of a patient of interest with patient data available at other clinical facilities participating in the network. Here, we present PatientMatcher (https://github.com/Clinical-Genomics/patientMatcher), an open-source Python and MongoDB-based software solution developed by Clinical Genomics facility at the Science for Life Laboratory in Stockholm. PatientMatcher is designed as a standalone MME server, but can easily communicate via REST API with external applications managing genetic analyses and patient data. The MME node is being implemented in clinical routine in collaboration with the Genomic Medicine Center Karolinska at the Karolinska University Hospital. PatientMatcher is written to implement the MME API and provides several customizable settings, including a custom-fit similarity score algorithm and adjustable matching results notifications.", "doi": "10.1002/humu.24358", "pmid": "35192731", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9311682"}], "notes": [], "created": "2026-09-23T12:55:50.429Z", "modified": "2026-09-23T12:55:50.558Z"}, {"entity": "publication", "iuid": "ca4796af599d4c89974438e83007ced9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ca4796af599d4c89974438e83007ced9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ca4796af599d4c89974438e83007ced9"}}, "title": "Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study.", "authors": [{"family": "St\u00f6dberg", "given": "Tommy", "initials": "T", "orcid": "0000-0003-1242-5260", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d2bff0a2811940b9a2f48d320e75f0d6.json"}}, {"family": "Tomson", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0003-0554-5352", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0f8577c0a7a74ba69fa9aca9583168a1.json"}}, {"family": "Barbaro", "given": "Michela", "initials": "M"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Carlsson", "given": "Sofia", "initials": "S"}, {"family": "\u00c5mark", "given": "Per", "initials": "P"}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9ba593bf3e472fa7d157cd697c7427.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Epilepsia", "issn": "1528-1167", "volume": "61", "issue": "11", "pages": "2486-2499", "issn-l": "0013-9580"}, "abstract": "Population-based data on epilepsy syndromes and etiologies in early onset epilepsy are scarce. The use of next-generation sequencing (NGS) has hitherto not been reported in this context. The aim of this study is to describe children with epilepsy onset before 2 years of age, and to explore to what degree whole exome and whole genome sequencing (WES/WGS) can help reveal a molecular genetic diagnosis.\n\nChildren presenting with a first unprovoked epileptic seizure before age 2 years and registered in the Stockholm Incidence Registry of Epilepsy (SIRE) between September 1, 2001 and December 31, 2006, were retrieved and their medical records up to age 7 years reviewed. Children who met the epilepsy criteria were included in the study cohort. WES/WGS was offered in cases of suspected genetic etiology regardless of whether a structural or metabolic diagnosis had been established.\n\nOne hundred sixteen children were included, of which 88 had seizure onset during the first year of life and 28 during the second, corresponding to incidences of 139 and 42/100 000 person-years, respectively. An epilepsy syndrome could be diagnosed in 54% of cases, corresponding to a birth prevalence of 1/1100. Structural etiology was revealed in 34% of cases, a genetic cause in 20%, and altogether etiology was known in 65% of children. The highest diagnostic yield was seen in magnetic resonance imaging (MRI) with 65% revealing an etiology. WES/WGS was performed in 26/116 cases (22%), with a diagnostic yield of 58%.\n\nEpilepsy syndromes can be diagnosed and etiologies revealed in a majority of early onset cases. NGS can identify a molecular diagnosis in a substantial number of children, and should be included in the work-up, especially in cases of epileptic encephalopathy, cerebral malformation, or metabolic disease without molecular diagnosis. A genetic diagnosis is essential to genetic counselling, prenatal diagnostics, and precision therapy.", "doi": "10.1111/epi.16701", "pmid": "32964447", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7756847"}], "notes": [], "created": "2026-09-23T09:28:18.576Z", "modified": "2026-09-23T09:28:18.751Z"}]}