{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:32:00Z","timestamp":1790040720757,"version":"4.0.1"},"reference-count":11,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:00:00Z","timestamp":1500940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Vascular Ehlers\u2013Danlos syndrome (type IV) is an autosomal dominant disorder caused by heterozygous variants of <jats:italic>COL3A1<\/jats:italic>. We identified biallelic <jats:italic>COL3A1<\/jats:italic> variants in two unrelated families. In a 3\u2010year\u2010old female with developmental delay the nonsense variant c.1282C&gt;T, p.(Arg428*) was detected in combination the c.2057delC, p.(Pro686Leufs*105) frame shift variant. Both compound heterozygous variants were novel. This patient was born with bilateral clubfoot, joint laxity, and dysmorphic facial features. At the age of 2 years she developed an aneurysmal brain hemorrhage. Cerebral MRI showed a peculiar pattern of profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family, the two affected siblings were homozygous for the missense variant c.145C&lt;G, p.(Pro49Ala) of <jats:italic>COL3A1<\/jats:italic> and showed cobblestone\u2010like cortical malformation, cerebellar cysts, and white matter abnormalities, developmental delay, and seizures. To date, three further families have been reported with biallelic variants of this gene and specific structural brain anomalies in all, and a severe Ehlers\u2013Danlos syndrome phenotype in some. Bilateral frontoparietal polymicrogyria of the cobblestone variant, cerebellar microcysts, and abnormalities of the white matter characterize this brain phenotype and resemble neurological manifestations in individuals with autosomal recessive mutations in <jats:italic>GPR56<\/jats:italic>, which serves as a ligand of <jats:italic>COL3A1<\/jats:italic>. In concordance with the findings in knock out mice, the collagen III protein plays a role in the regulation of cortical development in addition to its well\u2010known function in connective tissue formation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38345","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T12:32:51Z","timestamp":1500985971000},"page":"2534-2538","source":"Crossref","is-referenced-by-count":29,"title":["Biallelic <i>COL3A1<\/i> mutations result in a clinical spectrum of specific structural brain anomalies and connective tissue abnormalities"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0870-8911","authenticated-orcid":false,"given":"Denise","family":"Horn","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik und Humangenetik Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Siebert","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Neuroradiologie Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Seidel","sequence":"additional","affiliation":[{"name":"Kinderklinik, SPZ Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imma","family":"Rost","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Humangenetik und Laboratoriumsdiagnostik Martinsried Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Mayer","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Humangenetik und Laboratoriumsdiagnostik Martinsried Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Abou Jamra","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Leipzig Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Mitter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Hospital Leipzig Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Kornak","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Genetik und Humangenetik Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq259"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-32"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029767"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.181"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1852"},{"key":"e_1_2_6_7_1","volume-title":"Vascular Ehlers\u2013Danlos syndrome","author":"Pepin M. 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