{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:12Z","timestamp":1790524872263,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report a 38\u2010year\u2010old Saudi male with Ehlers\u2013Danlos Syndrome (EDS). The patient presented with rare and unusual neurological manifestations, including but not limited to ophthalmoplegia and myopathic pattern on his electromyography. In addition to hand weakness, there was skin hyperextensibility, joint hyperflexibility, and frontal baldness. Next\u2010generation sequencing was performed on target exon sequences, using whole exome sequencing and Burrows\u2013Wheeler Aligner for alignment\/base calling. Genome Analysis Toolkit and reference genome Homo sapiens (UCSC hg19) were used for sequence processing and analysis. Variant classification was done according to standard international recommendations. A novel homozygous variant, NM_019105.6: c.8488C&gt;T p.(Gln2830*), was detected in the <jats:italic>TNXB<\/jats:italic> gene. This variant is not reported in the literature nor dbSNP or gnomAD databases. Additionally, this variant is predicted to create a premature stop codon and produce a truncated protein or nonsense\u2010mediated mRNA decay. Hence, it is classified as a likely pathogenic variant. The same point variant was found in a heterozygous state in the patient's father and sister. Both presented with milder symptoms associated with Ehlers\u2013Danlos syndromes and heritable connective tissue disorders. Therefore, the patient was diagnosed as a tenascin\u2010X (TNX) deficient type of EDS known as classical\u2010like Ehlers\u2013Danlos syndrome. TNX deficient patients may present with clinical and electrophysiological manifestations that are unusual in EDS like frontal baldness, ophthalmoplegia, and myotonia, which mimic myotonic dystrophy type I. Clinicians should be aware of the potential overlap of symptoms among these two diseases to ensure correct diagnosis is made.<\/jats:p>","DOI":"10.1002\/ajmg.a.62539","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T15:02:53Z","timestamp":1634310173000},"page":"618-623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rare neurological manifestations in a Saudi Arabian patient with <scp>Ehlers\u2013Danlos<\/scp> syndrome and a novel homozygous variant in the <scp><i>TNXB<\/i><\/scp> gene"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5714-6789","authenticated-orcid":false,"given":"Talal M.","family":"Al\u2010Harbi","sequence":"first","affiliation":[{"name":"Neurology Department, Neuroscience Centre King Fahad Specialist Hospital\u2010Dammam  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Al\u2010Rammah","sequence":"additional","affiliation":[{"name":"Genetic Unit, Pathology and Laboratory Medicine Department King Fahad Specialist Hospital\u2010Dammam  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naif","family":"Al\u2010Zahrani","sequence":"additional","affiliation":[{"name":"Neurology Department, Neuroscience Centre King Fahad Specialist Hospital\u2010Dammam  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2023-072X","authenticated-orcid":false,"given":"Yichuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics (CAG) The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M. A.","family":"Sleiman","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics (CAG) The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics, The Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Dridi","sequence":"additional","affiliation":[{"name":"Genetic Unit, Pathology and Laboratory Medicine Department King Fahad Specialist Hospital\u2010Dammam  Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-7461","authenticated-orcid":false,"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics (CAG) The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics, The Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31547"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31550"},{"issue":"4","key":"e_1_2_9_4_1","first-page":"190","article-title":"Neurological manifestations of Ehlers\u2010Danlos syndrome(s): A review","volume":"13","author":"Castori M.","year":"2014","journal-title":"Iranian Journal of Neurology"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10080609"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-019-01894-0"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12853"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.1.123"},{"key":"e_1_2_9_9_1","first-page":"173","article-title":"Cutis laxa, neigung zu haemorrhagien in der haut, lockerung mehrerer artikulationen","volume":"8","author":"Ehlers E.","year":"1901","journal-title":"Dermatologische Zeitschrif"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.5496\/wjmg.v6.i2.17"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0028-3886.16938"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2013.92"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes10110843"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa002939"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz024"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62539","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62539","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62539","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T23:07:40Z","timestamp":1693004860000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,11]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1002\/ajmg.a.62539"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62539","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,11]]},"assertion":[{"value":"2020-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}