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To date, only five mutations in the proposed calcium-activated chloride channel <jats:italic>ANO5\/TMEM16E<\/jats:italic> gene have been identified. In this study, we describe two families and two singular patients with three new mutations. One Caucasian family with seven affected members exhibited frequent bone fractures and florid osseous dysplasia (p.Cys356Tyr), while one Chinese family with two affected members suffered from cementoma and purulent osteomyelitis (p.Cys360Tyr). In addition, two different novel mutations (p.Gly518Glu and p.Arg215Gly) were identified in sporadic patients without family history. <jats:italic>In vitro<\/jats:italic> studies overexpressing GDD mutations (p.Cys356Tyr and p.Cys360Tyr) showed significantly reduced ANO5 protein. It appears that all GDD mutations known so far locate in an extracellular domain following the first transmembrane domain or in the 4<jats:sup>th<\/jats:sup> putative transmembrane domain. Both wild-type and mutant ANO5 protein localize to the endoplasmic reticulum. After <jats:italic>Ano5<\/jats:italic> gene knock-down with shRNA in MC3T3-E1 osteoblast precursors we saw elevated expression of osteoblast-related genes such as <jats:italic>Col1a1, osteocalcin, osterix<\/jats:italic> and <jats:italic>Runx2<\/jats:italic> as well as increased mineral nodule formation in differentiating cells. Our data suggest that ANO5 plays a role in osteoblast differentiation.<\/jats:p>","DOI":"10.1038\/srep40935","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T11:53:09Z","timestamp":1486554789000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Three novel ANO5 missense mutations in Caucasian and Chinese families and sporadic cases with gnathodiaphyseal dysplasia"],"prefix":"10.1038","volume":"7","author":[{"given":"Lingling","family":"Jin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanyue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Blackwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert S.","family":"Woo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ernst J.","family":"Reichenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,2,8]]},"reference":[{"key":"BFsrep40935_CR1","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1359\/jbmr.2001.16.9.1710","volume":"16","author":"M Riminucci","year":"2001","unstructured":"Riminucci, M. et al. 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