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When more than one organ system is involved, a syndromic diagnosis is suspected. In this report, we describe three patients with apparently syndromic features. Exome sequencing identified non\u2010syndromic gene mutations as a potential cause of part of their phenotype. The first patient (Patient 1) is a girl with cleft lip\/palate, meningoencephalocele, tetralogy of Fallot, and developmental delay. The second and third patients (Patients 2 and 3) are brothers with developmental delay, deafness, and low bone mineral density. Exome sequencing revealed the presence of a <jats:italic>CDH1<\/jats:italic> mutation in Patient 1 and a <jats:italic>PLS3<\/jats:italic> mutation in Patients 2 and 3. <jats:italic>CDH1<\/jats:italic> mutations are known to be associated with non\u2010syndromic cleft lip\/palate, while <jats:italic>PLS3<\/jats:italic> mutations are associated with osteoporosis. Thus, these variants may explain a part of the complex phenotype of the patients, although the effects of these missense variants need to be evaluated by functional assays in order to prove pathogenicity. On the basis of these findings, we emphasize the importance of scrutinizing non\u2010syndromic gene mutations even in individuals with apparently syndromic features. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37826","type":"journal-article","created":{"date-parts":[[2016,8,27]],"date-time":"2016-08-27T04:40:40Z","timestamp":1472272840000},"page":"2889-2894","source":"Crossref","is-referenced-by-count":29,"title":["Exome sequencing\u2010based identification of mutations in non\u2010syndromic genes among individuals with apparently syndromic features"],"prefix":"10.1002","volume":"170","author":[{"given":"Eriko","family":"Nishi","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Nagano Children's Hospital Azumino Japan"},{"name":"Life Science Research Center Nagano Children's Hospital Azumino Japan"},{"name":"Department of Medical Genetics Shinshu University Graduate School of Medicine Matsumoto 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