title: Overlapping microdeletions involving 15q22.2 narrow the critical region for intellectual disability to NARG2 and RORA.
abstract: Microdeletions in the 15q22 region have not been well documented. We collected genotype and phenotype data from five patients with microdeletions involving 15q22.2, which were between 0.7 Mb and 6.5 Mb in size; two were of de novo origin and one was of familial origin. Intellectual disability and epilepsy are frequently observed in patients with 15q22.2 deletions. Genotype-phenotype correlation analysis narrowed the critical region for such neurologic symptoms to a genomic region of 654 Kb including the NMDA receptor-regulated 2 gene (NARG2) and the PAR-related orphan receptor A gene (RORA), either of which may be responsible for neurological symptoms commonly observed in patients with deletions in this region. The neighboring regions, including the forkhead box B1 gene (FOXB1), may also be related to the additional neurological features observed in the patients with larger deletions.
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
authors: Toshiyuki
authors: T
authors: Yamamoto
authors: Medical Genetics, University of Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors: Maria Antonietta
authors: MA
authors: Mencarelli
authors: Medical Genetics, University of Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors: Chiara
authors: C
authors: Di Marco
authors: Medical Genetics, University of Siena, Italy.
authors: Mafalda
authors: M
authors: Mucciolo
authors: Department of Pediatrics, Obstetrics, Gynecology, and Reproductive Medicine, Pediatric Neurology Unit, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy.
authors: Marina
authors: M
authors: Vascotto
authors: Department of Pediatrics, Obstetrics, Gynecology, and Reproductive Medicine, Pediatric Neurology Unit, S. Maria alle Scotte Hospital, University of Siena, Siena, Italy.
authors: Paolo
authors: P
authors: Balestri
authors: Laboratoire de Genetique Medicale, Hopital Jeanne de Flandre, CHRU, France.
authors: Marion
authors: M
authors: Gérard
authors: Laboratoire de Genetique Medicale, Hopital Jeanne de Flandre, CHRU, France.
authors: Michèle
authors: M
authors: Mathieu-Dramard
authors: Laboratoire de Genetique Medicale, Hopital Jeanne de Flandre, CHRU, France.
authors: Joris
authors: J
authors: Andrieux
authors: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Martijn
authors: M
authors: Breuning
authors: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Mariëtte J V
authors: MJ
authors: Hoffer
authors: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Claudia A L
authors: CA
authors: Ruivenkamp
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
authors: Shino
authors: S
authors: Shimada
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors: Noriko
authors: N
authors: Sangu
authors: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan.
authors: Keiko
authors: K
authors: Shimojima
authors: Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.
authors: Ryoji
authors: R
authors: Umezu
authors: Department of Genetic Counseling, Ochanomizu University, Tokyo, Japan; Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kawame
authors: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors: Mari
authors: M
authors: Matsuo
authors: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors: Kayoko
authors: K
authors: Saito
authors: Medical Genetics, University of Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors: Alessandra
authors: A
authors: Renieri
authors: Medical Genetics, University of Siena, Italy; Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors: Francesca
authors: F
authors: Mari
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics*; D010641:Phenotype; D035602:Transcriptional Elongation Factors; D055815:Young Adult
chemical_list: C501745:ICE2 protein, human; D009687:Nuclear Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D035602:Transcriptional Elongation Factors
keywords: 15q22.2; Epilepsy; Forkhead box B1 (FOXB1); Intellectual disability; Microdeletion; NMDA receptor-regulated 2 (NARG2); RAR-related orphan receptor A (RORA)