{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:46:01Z","timestamp":1778121961191,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Colony stimulating factor 1 receptor (<jats:italic>CSF1R<\/jats:italic>, MIM# 164770) encodes a tyrosine\u2010kinase receptor playing an important role in development of osteoclasts and microglia. Heterozygous <jats:italic>CSF1R<\/jats:italic> variants have been known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS, MIM# 221820), an adult\u2010onset leukoencephalopathy characterized by loss of motor functions and cognitive decline. Recently, a new phenotype characterized by brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) with biallelic <jats:italic>CSF1R<\/jats:italic> pathogenic variants in the etiology has been described. BANDDOS differs from HDLS by early\u2010onset neurodegenerative changes with additional structural brain abnormalities and skeletal findings resembling dysosteosclerosis (DOS). Described skeletal findings of the disease are highly variable ranging from absence of a skeletal phenotype and milder Pyle disease\u2010like to osteopetrosis and DOS. To date, only a few patients carrying biallelic <jats:italic>CSF1R<\/jats:italic> variants have been reported. In this clinical report, we describe three siblings with variable skeletal findings along with neurological symptoms ranging from mild to severe in whom exome sequencing revealed a novel homozygous splice site variant in canonical splice donor site of intron 21 adjacent to an exon, which encoding part of kinase domain of <jats:italic>CSF1R<\/jats:italic> along with a review of the literature.<\/jats:p>","DOI":"10.1002\/ajmg.a.62179","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T13:19:25Z","timestamp":1616419165000},"page":"1888-1896","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Further expanding the mutational spectrum of <scp>brain abnormalities, neurodegeneration, and dysosteosclerosis<\/scp>: A rare disorder with neurologic regression and skeletal features"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1416-7920","authenticated-orcid":false,"given":"Erdem","family":"K\u0131nd\u0131\u015f","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-7766","authenticated-orcid":false,"given":"Pelin \u00d6zlem","family":"Simsek\u2010Kiper","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-0510","authenticated-orcid":false,"given":"Can","family":"Ko\u015fukcu","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, Institute of Health Sciences Hacettepe University  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6040-6625","authenticated-orcid":false,"given":"Ekim Z.","family":"Ta\u015fk\u0131ran","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0223-9336","authenticated-orcid":false,"given":"Rah\u015fan","family":"G\u00f6\u00e7men","sequence":"additional","affiliation":[{"name":"Department of Radiology Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-5542","authenticated-orcid":false,"given":"Eda","family":"Utine","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1813-275X","authenticated-orcid":false,"given":"G\u00f6knur","family":"Halilo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6260-1942","authenticated-orcid":false,"given":"Koray","family":"Boduro\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"},{"name":"Department of Pediatric Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-062X","authenticated-orcid":false,"given":"Mehmet","family":"Alika\u015fifo\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"},{"name":"Department of Pediatric Genetics Hacettepe University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7509-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.040514"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026317"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR0519-143R"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509342"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006642"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20081605"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-014-0413-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.22"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61366"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.010"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1027"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(85)80047-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1228480"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0040-1702161"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.03.007"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.131"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62179","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62179","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T14:10:45Z","timestamp":1693577445000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/ajmg.a.62179"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62179","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"2021-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}