{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:33:22Z","timestamp":1785803602972,"version":"3.56.0"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T00:00:00Z","timestamp":1303776000000},"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":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cerebral cysts and calcifications with leukoencephalopathy and retinal vascular abnormalities are diagnostic hallmarks of cerebroretinal microangiopathy with calcifications and cysts (CRMCC). Previous studies have suggested that skeletal involvement is also common, but its characteristics remain unknown. This study aimed to assess the skeletal phenotype in CRMCC. All Finnish patients with features consistent with CRMCC and for whom radiographs were available were included. Clinical information pertinent to the skeletal phenotype was collected from hospital records, and all plain radiographs were reviewed for skeletal features. Bone mineral density (BMD) was measured by DXA. In one patient, bone biopsies were obtained for bone histology and histomorphometric analyses. The <jats:italic>LRP5<\/jats:italic> gene was analyzed for mutations by direct sequencing. Our results show that the skeletal phenotype in CRMCC includes (1) compromised longitudinal growth pre\u2010 and postnatally, (2) generalized osteopenia or early onset low turnover osteoporosis with fragility fractures, and (3) metaphyseal abnormalities that may lead to limb deformities such as short femoral neck or genua valga. DXA measurements in three patients showed low BMD, and bone biopsies in the fourth patient with pathological fractures and impaired fracture healing showed low\u2010turnover osteoporosis, with reduced osteoclast and osteoblast activity. Direct sequencing of all <jats:italic>LRP5<\/jats:italic> coding exons and exon\u2013intron boundaries in six patients with CRMCC revealed no putative mutations. We conclude that the CRMCC\u2010associated bone disease is characterized by low BMD and pathological fractures with delayed healing, metaphyseal changes, and short stature pre\u2010 and postnatally. <jats:italic>LRP5<\/jats:italic> is not a disease\u2010causing gene in CRMCC. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33994","type":"journal-article","created":{"date-parts":[[2011,4,26]],"date-time":"2011-04-26T20:11:28Z","timestamp":1303848688000},"page":"1322-1328","source":"Crossref","is-referenced-by-count":10,"title":["Cerebroretinal microangiopathy with calcifications and cysts: Characterization of the skeletal phenotype"],"prefix":"10.1002","volume":"155","author":[{"given":"Sanna","family":"Toiviainen\u2010Salo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarja","family":"Linnankivi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Saarinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervi K.","family":"M\u00e4yr\u00e4np\u00e4\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riitta","family":"Karikoski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,26]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1352"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32080"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652410791065345"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1093-180"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-43552"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(00)00074-8"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00257-4"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00571-2"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973451"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31819fd897"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000236999.63933.b0"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr. 373"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.01.012"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.29.9.673"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng957"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.11.010"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(01)00398-8"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1988.56"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/383202"}],"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.33994","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.33994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T18:08:09Z","timestamp":1697652489000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.33994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4,26]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,6]]}},"alternative-id":["10.1002\/ajmg.a.33994"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.33994","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4,26]]}}}