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Activity-dependent neuroprotective protein (\n                    <jats:italic>ADNP<\/jats:italic>\n                    ) is a most frequent\n                    <jats:italic>de novo<\/jats:italic>\n                    mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways. Here, collaborating with parents\/caregivers globally, we discovered premature tooth eruption as a potential early diagnostic biomarker for ADNP mutation. The parents of 44\/54 ADNP-mutated children reported an almost full erupted dentition by 1 year of age, including molars and only 10 of the children had teeth within the normal developmental time range. Looking at Adnp-deficient mice, by computed tomography, showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2 days, implicating age-dependent dysregulation of teething in Adnp-deficient mice. Allen Atlas analysis showed\n                    <jats:italic>Adnp<\/jats:italic>\n                    expression in the jaw area. RNA sequencing (RNAseq) and gene array analysis of human ADNP-mutated lymphoblastoids, whole-mouse embryos and mouse brains identified dysregulation of bone\/nervous system-controlling genes resulting from ADNP mutation\/deficiency (for example,\n                    <jats:italic>BMP1<\/jats:italic>\n                    and\n                    <jats:italic>BMP4<\/jats:italic>\n                    ).\n                    <jats:italic>AKAP6<\/jats:italic>\n                    , discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance. To the best of our knowledge, this is the first time that early primary (deciduous) teething is related to the ADNP syndrome, providing for early\/simple diagnosis and paving the path to early intervention\/specialized treatment plan.\n                  <\/jats:p>","DOI":"10.1038\/tp.2017.27","type":"journal-article","created":{"date-parts":[[2017,2,21]],"date-time":"2017-02-21T10:39:27Z","timestamp":1487673567000},"page":"e1043-e1043","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Premature primary tooth eruption in cognitive\/motor-delayed ADNP-mutated children"],"prefix":"10.1038","volume":"7","author":[{"given":"I","family":"Gozes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Van Dijck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Hacohen-Kleiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Grigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Karmon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Giladi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Eger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Gabet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pasmanik-Chor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Cappuyns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Elpeleg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R F","family":"Kooy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Bedrosian-Sermone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,21]]},"reference":[{"key":"BFtp201727_CR1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jaac.2013.10.013","volume":"53","author":"F Volkmar","year":"2014","unstructured":"Volkmar F, Siegel M, Woodbury-Smith M, King B, McCracken J, State M et al. 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