title: Exome sequencing-based identification of mutations in non-syndromic genes among individuals with apparently syndromic features.
abstract: In a clinical setting, the number of organ systems involved is crucial for the differential diagnosis of congenital genetic disorders. 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-syndromic 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 CDH1 mutation in Patient 1 and a PLS3 mutation in Patients 2 and 3. CDH1 mutations are known to be associated with non-syndromic cleft lip/palate, while PLS3 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-syndromic gene mutations even in individuals with apparently syndromic features. © 2016 Wiley Periodicals, Inc.
authors: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Department of Medical Genetics, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors: Eriko
authors: E
authors: Nishi
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors: Koji
authors: K
authors: Masuda
authors: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.
authors: Michiko
authors: M
authors: Arakawa
authors: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.
authors: Hiroshi
authors: H
authors: Kawame
authors: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.|Department of Medical Genetics, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors: Tomoki
authors: T
authors: Kosho
authors: Department of Pediatrics, Matsumoto Medical Center of Chu-shin-Matsumoto Hospital, Matsumoto, Japan.
authors: Masashi
authors: M
authors: Kitahara
authors: Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.
authors: Noriko
authors: N
authors: Kubota
authors: Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.
authors: Eiko
authors: E
authors: Hidaka
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Katoh
authors: Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors: Katsuhiko
authors: K
authors: Shirahige
authors: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan. izumik1@email.chop.edu.|Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan. izumik1@email.chop.edu.|Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. izumik1@email.chop.edu.
authors: Kosuke
authors: K
authors: Izumi
mesh_terms: D000328:Adult; D015703:Antigens, CD; D001921:Brain / Q000473:pathology; D015820:Cadherins / Q000737:chemistry / Q000235:genetics; D002648:Child; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D059472:Exome; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D013577:Syndrome
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins
keywords: CDH1; PLS3; cleft lip; cleft palate; osteoporosis