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We report a novel Arg5Trp missense mutation in the<jats:italic>PITX2<\/jats:italic>homeodomain, which is associated with brain abnormalities. One patient had a small sella turcica likely to reflect hypoplasia of the pituitary gland and consistent with the critical role identified for<jats:italic>Pitx2<\/jats:italic>in pituitary development in mice. Two patients had an enlarged cisterna magna, one with a malformed cerebellum, and two had executive skills deficits one in isolation and one in association with a below average intellectual capacity. The mutation caused a typical ARS ocular phenotype. All affected had iris hypoplasia, anterior iris to corneal adhesions, and corectopia. The ocular phenotype varied significantly in severity and showed some asymmetry. All affected also had redundant peri\u2010umbilical skin, a hypoplastic maxilla, microdontia, and hypodontia missing between 20 and 27 teeth with an unusual pattern of tooth loss. Dental phenotypes were documented as they are often poorly characterized in ARS patients. All affected individuals showed an absence of first permanent molars with variable absence of other rarely absent teeth: the permanent upper central incisors, maxillary and mandibular first and second molars, and the mandibular canines. Based on the distinctive dental anomalies, we suggest that the dental phenotype can assist in predicting the presence of a<jats:italic>PITX2<\/jats:italic>mutation and the possibility of brain abnormalities. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.30237","type":"journal-article","created":{"date-parts":[[2006,1,2]],"date-time":"2006-01-02T17:16:27Z","timestamp":1136222187000},"page":"184-191","source":"Crossref","is-referenced-by-count":35,"title":["A novel homeobox mutation in the<i>PITX2<\/i>gene in a family with Axenfeld\u2010Rieger syndrome associated with brain, ocular, and dental phenotypes"],"prefix":"10.1002","volume":"141B","author":[{"given":"Faisal","family":"Idrees","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Bloch\u2010Zupan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha 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