title: Novel splicing mutation in the ASXL3 gene causing Bainbridge-Ropers syndrome.
abstract: Bainbridge-Ropers syndrome (BRPS) is characterized by severe developmental delay, feeding problems, short stature, characteristic facal appearance including arched eyebrows and anteverted nares, and ulnar deviation of the hands. BRPS is caused by a heterozygous mutation in the additional sex combs-like 3 (ASXL3) gene. We describe a patient with severe developmental delay, feeding problems, short stature, autism, and sleep disturbance with a heterozygous de novo splicing mutation in the ASXL3 gene. Reported disease-causing mutations in ASXL3 are located mostly in the first half of exon 11, analogous to ASXL1 mutations of which result in Bohring-Opitz syndrome (BOS). Our findings suggest that the expression of the truncated ASXL3 protein, including ASXN and ASXH domains, give rise to BRPS, which is distinct from but overlaps with BOS. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Hori
authors.affiliation: Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Miya
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Negishi
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Hattori
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ando
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Department of Neurosurgery, Takatsuki General Hospital, Osaka, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Division of Regenerative Medicine, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan.|Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
authors.forename: Yonehiro
authors.initials: Y
authors.lastname: Kanemura
authors.affiliation: Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kosaki
authors.affiliation: Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
mesh_terms: D002675:Child, Preschool; D003398:Craniosynostoses / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D002658:Developmental Disabilities / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D012097:Repressor Proteins
chemical_list: D014157:Transcription Factors; C494423:ASXL3 protein, human; D012097:Repressor Proteins
keywords: ASXL3; Bainbridge-Ropers syndrome; whole-exome sequencing