{"entity": "researcher", "timestamp": "2026-07-20T13:04:54.903Z", "family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "affiliations": ["Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala, Sweden. joakim.klar@igp.uu.se.", "Department of Women's and Children's Health, Section of Pediatric Surgery, Uppsala University, SE-75185, Uppsala, Sweden. joakim.klar@igp.uu.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83"}}, "publications": [{"entity": "publication", "iuid": "3f9436baa42849ed95e219bbf949416e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3f9436baa42849ed95e219bbf949416e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3f9436baa42849ed95e219bbf949416e"}}, "title": "Whole genome sequencing of familial isolated oesophagus atresia uncover shared structural variants.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Engstrand-Lilja", "given": "Helene", "initials": "H"}, {"family": "Maqbool", "given": "Khurram", "initials": "K"}, {"family": "Mattisson", "given": "Jonas", "initials": "J"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2020-06-26", "journal": {"title": "BMC Med Genomics", "issn": "1755-8794", "volume": "13", "issue": "1", "pages": "85", "issn-l": "1755-8794"}, "abstract": "Oesophageal atresia (OA) is a life-threatening developmental defect characterized by a lost continuity between the upper and lower oesophagus. The most common form is a distal connection between the trachea and the oesophagus, i.e. a tracheoesophageal fistula (TEF). The condition may be part of a syndrome or occurs as an isolated feature. The recurrence risk in affected families is increased compared to the population-based incidence suggesting contributing genetic factors.\n\nTo gain insight into gene variants and genes associated with isolated OA we conducted whole genome sequencing on samples from three families with recurrent cases affected by congenital and isolated TEF.\n\nWe identified a combination of single nucleotide variants (SNVs), splice site variants (SSV) and structural variants (SV) annotated to altogether 100 coding genes in the six affected individuals.\n\nThis study highlights rare SVs among candidate gene variants in our individuals with OA and provides a gene framework for further investigations of genetic factors behind this malformation.", "doi": "10.1186/s12920-020-00737-6", "pmid": "32586322", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12920-020-00737-6"}, {"db": "pmc", "key": "PMC7318369"}], "notes": [], "created": "2020-07-03T05:25:29.915Z", "modified": "2024-01-16T13:48:42.333Z"}, {"entity": "publication", "iuid": "63a924bcbe104548a3e5ceccc51815f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/63a924bcbe104548a3e5ceccc51815f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/63a924bcbe104548a3e5ceccc51815f5"}}, "title": "Stereocilin gene variants associated with episodic vertigo: expansion of the DFNB16 phenotype.", "authors": [{"family": "Frykholm", "given": "Carina", "initials": "C"}, {"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Tomanovic", "given": "Tatjana", "initials": "T"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "case reports", "published": "2018-12-00", "journal": {"volume": "26", "issn": "1476-5438", "issue": "12", "title": "Eur. J. Hum. Genet.", "pages": "1871-1874", "issn-l": "1018-4813"}, "abstract": "Vestibular disorders comprise a heterogeneous group of diseases with transient or permanent loss of vestibular function. Vestibulopathy is in most cases associated with migraine, M\u00e9ni\u00e8re disease, hereditary ataxias, or sensorineural hearing loss. We identified two brothers and their first cousin affected by hearing loss and episodic vertigo. The brothers were homozygous STRC nonsense variant [c.4027 C > T, p.(Q1343*)], whereas their first cousin was compound heterozygous for the STRC nonsense variant and a 97 kb deletion spanning the entire STRC gene. Clinical investigations confirmed pathological vestibular responses in addition to a characteristic DFNB16 hearing loss. The STRC gene encodes Stereocilin in the cochlea and in the vestibular organ where it ensheathes the kinocilium of the otolithic membranes. Stereocilin is associated with the gel overlaying the vestibular kinocilia, suggesting a role for the protein in sensing balance and spatial orientation. Our findings support such a function for Stereocilin in the vestibular organ and expand the phenotype associated with DFNB16.", "doi": "10.1038/s41431-018-0256-6", "pmid": "30250054", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-018-0256-6"}, {"db": "pmc", "key": "PMC6244415"}], "notes": [], "created": "2018-11-08T13:16:49.023Z", "modified": "2024-01-16T13:48:44.990Z"}, {"entity": "publication", "iuid": "8debe2b674394b34846e436ba217e239", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8debe2b674394b34846e436ba217e239.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8debe2b674394b34846e436ba217e239"}}, "title": "SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts.", "authors": [{"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}, {"family": "Henning", "given": "Petra", "initials": "P"}, {"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "McDermott", "given": "Emma", "initials": "E"}, {"family": "Stecksen-Blicks", "given": "Christina", "initials": "C"}, {"family": "Sandstr\u00f6m", "given": "Per-Erik", "initials": "PE"}, {"family": "Kellgren", "given": "Therese G", "initials": "TG"}, {"family": "Ryd\u00e9n", "given": "Patrik", "initials": "P"}, {"family": "Hallmans", "given": "G\u00f6ran", "initials": "G"}, {"family": "L\u00f6nnerholm", "given": "Torsten", "initials": "T"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Helfrich", "given": "Miep H", "initials": "MH"}, {"family": "Coxon", "given": "Fraser P", "initials": "FP"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}, {"family": "Wikstr\u00f6m", "given": "Johan", "initials": "J"}, {"family": "Lerner", "given": "Ulf H", "initials": "UH"}], "type": "journal article", "published": "2017-06-07", "journal": {"volume": "7", "issn": "2045-2322", "issue": "1", "pages": "3012", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Autosomal recessive osteopetrosis (ARO) is a heterogeneous disorder, characterized by defective osteoclastic resorption of bone that results in increased bone density. We have studied nine individuals with an intermediate form of ARO, from the county of V\u00e4sterbotten in Northern Sweden. All afflicted individuals had an onset in early infancy with optic atrophy, and in four patients anemia was present at diagnosis. Tonsillar herniation, foramen magnum stenosis, and severe osteomyelitis of the jaw were common clinical features. Whole exome sequencing, verified by Sanger sequencing, identified a splice site mutation c.212 + 1 G > T in the SNX10 gene encoding sorting nexin 10. Sequence analysis of the SNX10 transcript in patients revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). Haplotype analysis showed that all cases originated from a single mutational event, and the age of the mutation was estimated to be approximately 950 years. Functional analysis of osteoclast progenitors isolated from peripheral blood of patients revealed that stimulation with receptor activator of nuclear factor kappa-B ligand (RANKL) resulted in a robust formation of large, multinucleated osteoclasts which generated sealing zones; however these osteoclasts exhibited defective ruffled borders and were unable to resorb bone in vitro.", "doi": "10.1038/s41598-017-02533-2", "pmid": "28592808", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-02533-2"}, {"db": "pmc", "key": "PMC5462793"}], "notes": [], "created": "2017-10-30T13:36:01.438Z", "modified": "2024-01-16T13:48:47.879Z"}, {"entity": "publication", "iuid": "75eed86d1a72489e8579fbd105541c14", "links": {"self": {"href": "https://publications.scilifelab.se/publication/75eed86d1a72489e8579fbd105541c14.json"}, "display": {"href": "https://publications.scilifelab.se/publication/75eed86d1a72489e8579fbd105541c14"}}, "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.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Raykova", "given": "Doroteya", "initials": "D", "orcid": "0000-0001-6452-2199", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a81c40491e349178167f148f2351875.json"}}, {"family": "Gustafson", "given": "Elisabet", "initials": "E"}, {"family": "T\u00f3thov\u00e1", "given": "Iveta", "initials": "I"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Wanders", "given": "Alkwin", "initials": "A"}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2015-12-00", "journal": {"volume": "23", "issn": "1476-5438", "issue": "12", "pages": "1679-1683", "title": "Eur. J. Hum. Genet.", "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": {"National Genomics Infrastructure": null, "NGI Uppsala (Uppsala Genome Center)": null}, "xrefs": [{"db": "pii", "key": "ejhg201549"}, {"db": "pmc", "key": "PMC4795199"}], "notes": [], "created": "2017-05-02T12:57:23.795Z", "modified": "2021-07-07T14:37:06.508Z"}]}