title: De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux.
abstract: MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change-specifically, an in-frame MEIS2 deletion-has so far been reported. Here, we report a female patient with a de novo nonsense mutation (c.611C>G, p.Ser204*) in MEIS2. She showed severe intellectual disability, moderate motor/verbal developmental delay, cleft palate, cardiac septal defect, hypermetropia, severe feeding difficulties with gastro-esophageal reflux and constipation. By reviewing this patient and previous patients with MEIS2 point mutations, we found that feeding difficulty with gastro-esophageal reflux appears to be one of the core clinical features of MEIS2 haploinsufficiency, in addition to intellectual disability, cleft palate and cardiac septal defect.
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujita
authors.affiliation: Service de Génétique Médicale, CHU de Nantes, Nantes, France.|INSERM, UMR-S 957, Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Service de Pédiatrie, CHU de Nantes, Nantes, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Piloquet
authors.affiliation: Service de Stomatologie, CHU de Nantes, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Corre
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 Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Hirotomo
authors.identifier: http://orcid.org/0000-0003-0723-0960
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome; D019066:Facies; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000235:genetics*; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation; D010641:Phenotype; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C491172:MEIS2 protein, human; D014157:Transcription Factors