{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:43:03Z","timestamp":1791398583348,"version":"4.3.3"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T00:00:00Z","timestamp":1376611200000},"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":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Proteoglycans are a component of the extracellular matrix and are critical for cellular and tissue function. Mutations in proteoglycan components and enzymes involved in proteoglycan synthesis have been implicated in several growth disorders, with common features including short stature and skeletal dysplasia. For example, mutations in <jats:italic>B4GALT7<\/jats:italic>, a gene whose protein product catalyzes proteoglycan synthesis, have been associated with the rare progeroid variant of Ehlers\u2013Danlos syndrome. Here, we conducted exome sequencing in a patient with a previously undiagnosed growth disorder and identified compound heterozygous mutations in <jats:italic>B4GALT7<\/jats:italic>. This patient is just the fourth individual with genetically confirmed progeroid variant of Ehlers\u2013Danlos syndrome. The mutations include a previously characterized c.808C&gt;T p.Arg270Cys substitution, and a novel c.122T&gt;C p.Leu41Pro substitution. We demonstrate that the novel mutation caused decreased levels of the enzyme, supporting the pathogenicity of the mutation. Our report identifies a novel mutation in <jats:italic>B4GALT7<\/jats:italic> causing the progeroid variant of Ehlers\u2013Danlos syndrome and contributes an extensive phenotypic characterization of a patient with the syndrome. We also reviewed the previous literature in addition to the present patient, and conclude that the key features associated with <jats:italic>B4GALT7<\/jats:italic> deficiency are short stature, developmental anomalies of the forearm bones and elbow, and bowing of the extremities, in addition to the classic features of Ehlers\u2013Danlos syndrome. This report helps define the phenotype of the progeroid variant of Ehlers\u2013Danlos syndrome and furthers our understanding of the effect of proteoglycan defects in growth disorders. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36128","type":"journal-article","created":{"date-parts":[[2013,8,16]],"date-time":"2013-08-16T17:33:09Z","timestamp":1376674389000},"page":"2519-2527","source":"Crossref","is-referenced-by-count":46,"title":["Redefining the progeroid form of ehlers\u2013danlos syndrome: Report of the fourth patient with <i>B4GALT7<\/i> deficiency and review of the literature"],"prefix":"10.1002","volume":"161","author":[{"given":"Michael H.","family":"Guo","sequence":"first","affiliation":[{"name":"Program in Biological and Biomedical Sciences Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Stoler","sequence":"additional","affiliation":[{"name":"Division of Genetics Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Lui","sequence":"additional","affiliation":[{"name":"Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Program in Developmental Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda Maryland"},{"name":"Department of Women's and Children's Health Center for Molecular Medicine and Pediatric Endocrinology Unit Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana W.","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Mother Infant Research Institute Tufts Medical Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Hirschhorn","sequence":"additional","affiliation":[{"name":"Department of Genetics Harvard Medical School Boston Massachusetts"},{"name":"Division of Endocrinology Boston Children's Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Dauber","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Boston Children's Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,16]]},"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":"10.1074\/jbc.274.37.26165"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.05.021"},{"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.jpeds.2012.07.055"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00256-009-0762-2"},{"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":"10.1136\/jmg.38.7.430"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1894"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-005-1068-2"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm372"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1681"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1986.tb01910.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1981.tb01833.x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1979.tb01012.x"},{"key":"e_1_2_6_17_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_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds347"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.28841"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.2.193"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.4.1342"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100921"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-006-0046-4"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000410)91:4<280::AID-AJMG8>3.0.CO;2-B"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400334101"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.005"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2005.063040"}],"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.36128","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T23:00:52Z","timestamp":1696633252000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,16]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1002\/ajmg.a.36128"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36128","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,8,16]]}}}