{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:43:30Z","timestamp":1790027010759,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T00:00:00Z","timestamp":1434585600000},"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":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Linkeropathies are a group of syndromes characterized by short stature, radio\u2010ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by<jats:italic>B3GAT3<\/jats:italic>, adds the last four saccharides comprising the linker region. Mutations in<jats:italic>B3GAT3<\/jats:italic>have been reported in two unrelated families with the same homozygous mutation (c.830G&gt;A, p.Arg277Gln). We report on a patient with a novel homozygous<jats:italic>B3GAT3<\/jats:italic>(c.667G&gt;A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12\u2010month\u2010old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio\u2010ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra\u2010 and infratentorial subdural hematomas. We highlight the extended phenotypic range of<jats:italic>B3GAT3<\/jats:italic>mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in<jats:italic>XYLT1<\/jats:italic>,<jats:italic>B4GALT7<\/jats:italic>,<jats:italic>B3GALT6<\/jats:italic>, and<jats:italic>B3GAT3<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37209","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T11:04:08Z","timestamp":1434625448000},"page":"2691-2696","source":"Crossref","is-referenced-by-count":52,"title":["A homozygous<i>B3GAT3<\/i>mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes"],"prefix":"10.1002","volume":"167","author":[{"given":"Kelly L.","family":"Jones","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington &amp; Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schwarze","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret P.","family":"Adam","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington &amp; Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Byers","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington Seattle Washington"},{"name":"Department of Medicine University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather C.","family":"Mefford","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Department of Pediatrics University of Washington &amp; Seattle Children's Hospital Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,18]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.021"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.729"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05817"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.01.020"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.60"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30005"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1894"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1002\/ajmg.a.36128","article-title":"Redefining the progeroid form of Ehlers\u2013Danlos syndrome: Report of the fourth patient with B4GALT7 deficiency and review of the literature","volume":"161","author":"Guo MH","year":"2013","journal-title":"Am J Med Genet Part A"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411552200"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1681"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.074043"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.6615"},{"key":"e_1_2_6_15_1","first-page":"436","article-title":"Glycosaminoglycan\u2010free small proteoglycan core protein is secreted by fibroblasts from a patient with a syndrome resembling progeroid","volume":"41","author":"Kresse H","year":"1987","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.016"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.003"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611665200"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1351-y"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04849.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36487"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37209","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37209","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T15:43:47Z","timestamp":1717947827000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37209"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,18]]},"references-count":20,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1002\/ajmg.a.37209"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37209","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,18]]}}}