{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:51:38Z","timestamp":1769093498059,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T00:00:00Z","timestamp":1525651200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000871","name":"Newlife Foundation for Disabled Children","doi-asserted-by":"publisher","award":["SG\/14\u201015\/05"],"award-info":[{"award-number":["SG\/14\u201015\/05"]}],"id":[{"id":"10.13039\/501100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone\u2010mass.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patient 1: 40\u2010year old adult male diagnosed with IJO in childhood who re\u2010presented with a hip fracture as an adult. Genetic analysis identified a pathogenic <jats:italic>PLS3<\/jats:italic> hemizygous variant, c.1765del in exon 16. Patient 2: 15\u2010year old boy with multiple vertebral fractures and bone biopsy findings suggestive of IJO who also has a diagnosis of autism spectrum disorder. Genetic analysis identified a maternally inherited <jats:italic>PLS3<\/jats:italic> pathogenic c.1295T&gt;A variant in exon 12. Analyses of the transiliac bone sample revealed severe reduction of trabecular volume and bone turnover indices and elevated bone matrix mineralisation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We propose that genetic testing for <jats:italic>PLS3<\/jats:italic> should be undertaken in patients presenting with a current or previous history of IJO as this has implications for genetic counselling and cascade screening. The extensive evaluation of the transiliac biopsy sample of Patient 2 revealed a novel bone phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This report includes a review of IJO and genetic causes of osteoporosis, and suggests that existing cases of IJO should be screened for <jats:italic>PLS3<\/jats:italic>. Through analysis of bone material properties in Patient 2, we can conclude that <jats:italic>PLS3<\/jats:italic> does have a role in bone mineralisation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38830","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T06:27:55Z","timestamp":1525760875000},"page":"1578-1586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Novel <i>PLS3<\/i> variants in X\u2010linked osteoporosis: Exploring bone material properties"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1488-3695","authenticated-orcid":false,"given":"Meena","family":"Balasubramanian","sequence":"first","affiliation":[{"name":"Highly Specialised Severe, Complex &amp; Atypical OI Service Sheffield Children's NHS Foundation Trust  UK"},{"name":"Sheffield Clinical Genetics Service Sheffield Children's NHS Foundation Trust  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja","family":"Fratzl\u2010Zelman","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1<sup>st<\/sup> Med. Dept. Hanusch Hospital 1140 Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rory","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Medical School University of Sheffield  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Bull","sequence":"additional","affiliation":[{"name":"Metabolic Bone Centre Northern General Hospital Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"FA Peel","sequence":"additional","affiliation":[{"name":"Metabolic Bone Centre Northern General Hospital Sheffield UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8864-397X","authenticated-orcid":false,"given":"Rebecca C","family":"Pollitt","sequence":"additional","affiliation":[{"name":"Sheffield Diagnostic Genetics Service Sheffield Children's NHS Foundation Trust  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Psychology Sheffield Children's NHS Foundation Trust  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Milne","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Sheffield  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kath","family":"Smith","sequence":"additional","affiliation":[{"name":"Sheffield Diagnostic Genetics Service Sheffield Children's NHS Foundation Trust  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Roschger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1<sup>st<\/sup> Med. Dept. Hanusch Hospital 1140 Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Klaushofer","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1<sup>st<\/sup> Med. Dept. Hanusch Hospital 1140 Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J","family":"Bishop","sequence":"additional","affiliation":[{"name":"Academic Unit of Child Health University of Sheffield  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9814928"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2835"},{"key":"e_1_2_8_4_1","unstructured":"Dalgleish R.(2017).Osteogenesis Imperfecta Variant Database: PLS3. 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