{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T02:46:29Z","timestamp":1777430789600,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T00:00:00Z","timestamp":1492992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008664","name":"Juvenile Diabetes Research Foundation","doi-asserted-by":"publisher","award":["3\u2010PDF\u20102014\u2010186\u2010A\u2010N"],"award-info":[{"award-number":["3\u2010PDF\u20102014\u2010186\u2010A\u2010N"]}],"id":[{"id":"10.13039\/100008664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Heterozygous mutations in the genes encoding the pro\u03b11(I) or pro\u03b12(I) chains of type I procollagen (<jats:italic>COL1A1<\/jats:italic> and <jats:italic>COL1A2<\/jats:italic>, respectively) account for most cases of osteogenesis imperfecta (OI), a disorder characterized by reduced bone strength and increased fracture risk. <jats:italic>COL1A1<\/jats:italic> mutations can also cause rare cases of Ehlers\u2013Danlos syndrome (EDS), a disorder that primarily affects connective tissue and often includes reduced bone mass. Here we present a kindred of three young siblings ages 1\u20134 years old whose mother has a history of mild type I OI. All three children are compound heterozygotes for <jats:italic>COL1A1<\/jats:italic> mutations, with a novel frameshift mutation (c.2522delC; p.Pro841Leufs*266) from their mother and a known missense mutation (c.3196C&gt;T; p.R1066C) from their clinically unaffected father, which has previously been described as causing a combined type I OI\/EDS phenotype. The three children exhibit features of both <jats:italic>COL1A1<\/jats:italic> mutations: early and frequent long bone fractures, joint hyperextensibility, and blue sclerae. We describe three siblings who are the first reported surviving subjects with biallelic pathogenic <jats:italic>COL1A1<\/jats:italic> mutations. They have a more severe form of type I OI with features of EDS that represents their compound heterozygosity for two deleterious <jats:italic>COL1A1<\/jats:italic> mutations. Their long\u2010term outcomes are yet to be determined.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38238","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T07:28:11Z","timestamp":1493018891000},"page":"1907-1912","source":"Crossref","is-referenced-by-count":12,"title":["Compound heterozygous mutations in <i>COL1A1<\/i> associated with an atypical form of type I osteogenesis imperfecta"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-9790","authenticated-orcid":false,"given":"Amanda M.","family":"Ackermann","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia and Department of Pediatrics Perelman School of Medicine of the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Levine","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia and Department of Pediatrics Perelman School of Medicine of the University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1942"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971003)72:1<94::AID-AJMG20>3.0.CO;2-O"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20456"},{"key":"e_1_2_8_5_1","unstructured":"Dalgleish R.(2015). Osteogenesis Imperfecta Variant Database. Leiden Open Variation Database v.2.0 Build 36."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2012.01858.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050392"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22760"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2680"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1403"},{"issue":"2","key":"e_1_2_8_12_1","first-page":"140","article-title":"Analysis of type IV osteogenesis imperfecta caused by two mutations occurred simultaneously in COL1A1 gene in a Chinese child","volume":"33","author":"Ju M.","year":"2016","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1730"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2016.11.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"issue":"35","key":"e_1_2_8_16_1","doi-asserted-by":"crossref","first-page":"25521","DOI":"10.1016\/S0021-9258(19)74071-X","article-title":"Type I procollagens containing substitutions of aspartate, arginine, and cysteine for glycine in the pro alpha 1 (I) chain are cleaved slowly by N\u2010proteinase, but only the cysteine substitution introduces a kink in the molecule","volume":"267","author":"Lightfoot S. J.","year":"1992","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.038224"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.12.030"},{"key":"e_1_2_8_19_1","unstructured":"OMIM\u00ae.2016. Online Mendelian Inheritance in Man. McKusick\u2010Nathans Institute of Genetic Medicine Johns Hopkins University. Baltimore MD:http:\/\/omim.org\/."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2567"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.16.2.101"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(99)00056-6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22677"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37051"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36545"},{"issue":"4","key":"e_1_2_8_26_1","first-page":"799","article-title":"Premature chain termination is a unifying mechanism for COL1A1 null alleles in osteogenesis imperfecta type I cell strains","volume":"59","author":"Willing M. 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