{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T22:36:29Z","timestamp":1775514989577,"version":"3.50.1"},"reference-count":7,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T00:00:00Z","timestamp":1563753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation for Young Scientists of Shanxi Province, China","award":["201801D221248"],"award-info":[{"award-number":["201801D221248"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Beta\u2010propeller protein\u2010associated neurodegeneration (BPAN, OMIM 300894) is an X\u2010linked neurodegenerative disorder caused by mutations in <jats:italic>WDR45<\/jats:italic>. WDR45 is required for autophagy, defect in WDR45 impaired autophagy which contributes for the pathogenesis of BPAN. Previously, we reported a novel de novo mutation (c.1040_1041del, p.Glu347GlyfsTer7) in <jats:italic>WDR45<\/jats:italic> (NM_007075) in a 3\u2010year\u2010old Chinese girl with BPAN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The protein structure was constructed using SWISS\u2010MODEL and the isoelectric point (pI) was predicted by the online pI\/Mw tool at ExPASy. The functional effects of this mutation were predicted by two online software programs: PROVEN and MutationTaster. Stable overexpression of Flag\u2010tagged wild\u2010type or mutant <jats:italic>WDR45<\/jats:italic> in HeLa cells was constructed. Protein levels of LC3 and p62 were analyzed by western blot upon treatment with\/without autophagy inhibitor Bafilomycin A1, the formation of LC3 puncta were analyzed in HeLa cells transfected with mCherry\u2010LC3 by confocal microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mutation resulted in a shift of pI from 6.74 to 8.84 and was predicted to be pathogenic. The protein levels of LC3\u2010II and p62 were increased in cells overexpression of wild\u2010type and mutant <jats:italic>WDR45<\/jats:italic> while the protein levels were not increased in cells overexpression of mutant <jats:italic>WDR45<\/jats:italic> upon treatment with autophagy inhibitor Bafilomycin A1. Results from confocal microscopy revealed that LC3\u2010positive puncta were increased in cells expressing both wild\u2010type and mutant <jats:italic>WDR45<\/jats:italic> while the number of LC3\u2010positive puncta was not increased in cells expressing mutant <jats:italic>WDR45<\/jats:italic> upon treatment with Bafilomycin A1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study evidenced that this novel mutation in <jats:italic>WDR45<\/jats:italic> impaired autophagy in cells thus this mutation is the cause for BPAN in this patient.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.858","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T01:39:01Z","timestamp":1563845941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Functional evidence for a de novo mutation in <i>WDR45<\/i> leading to BPAN in a Chinese girl"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-7353","authenticated-orcid":false,"given":"Qiuhong","family":"Xiong","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Science Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Science Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-6154","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Science Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhonghua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Science Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Science Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Science Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15637"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046688"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.10.019"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.02.019"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2562"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"issue":"4","key":"e_1_2_6_8_1","first-page":"381","article-title":"Novel de novo mutaion in tha autophagy gene WDR45 causes BOAN in a Chinese family","volume":"12","author":"Xiao H.","year":"2018","journal-title":"Journal of Molecular and Genetic Medicine"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmgg3.858","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.858","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.858","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T00:30:20Z","timestamp":1694219420000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,22]]},"references-count":7,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/mgg3.858"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.858","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,22]]},"assertion":[{"value":"2019-02-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e858"}}