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Patient\u2010derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients showed biallelic mutations in the nonclustered <jats:italic>protocadherin\u201012<\/jats:italic> (<jats:italic>PCDH12<\/jats:italic>) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of <jats:italic>PCDH12<\/jats:italic> in neural and endothelial cells. These cells showed lack of <jats:italic>PCDH12<\/jats:italic> expression and impaired neurite outgrowth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>DMJD patients have biallelic mutations in <jats:italic>PCDH12<\/jats:italic> and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with <jats:italic>PCDH12<\/jats:italic>\u2010related conditions. Ann Neurol 2018;84:638\u2013647<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25327","type":"journal-article","created":{"date-parts":[[2018,9,4]],"date-time":"2018-09-04T04:25:05Z","timestamp":1536035105000},"page":"638-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Loss of <i>Protocadherin\u201012<\/i><scp>L<\/scp>eads to <scp>D<\/scp>iencephalic\u2010<scp>M<\/scp>esencephalic <scp>J<\/scp>unction <scp>D<\/scp>ysplasia <scp>S<\/scp>yndrome"],"prefix":"10.1002","volume":"84","author":[{"given":"Alicia","family":"Guemez\u2010Gamboa","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Laboratory for Pediatric Brain Disease Rockefeller University  New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet Okay","family":"\u00c7a\u011flayan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Yale School of Medicine  New Haven 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