title: Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.
abstract: Mutations in FOXP2 cause developmental verbal dyspraxia (DVD), but only a few cases have been described. We characterize 13 patients with DVD--5 with hemizygous paternal deletions spanning the FOXP2 gene, 1 with a translocation interrupting FOXP2, and the remaining 7 with maternal uniparental disomy of chromosome 7 (UPD7), who were also given a diagnosis of Silver-Russell Syndrome (SRS). Of these individuals with DVD, all 12 for whom parental DNA was available showed absence of a paternal copy of FOXP2. Five other individuals with deletions of paternally inherited FOXP2 but with incomplete clinical information or phenotypes too complex to properly assess are also described. Four of the patients with DVD also meet criteria for autism spectrum disorder. Individuals with paternal UPD7 or with partial maternal UPD7 or deletion starting downstream of FOXP2 do not have DVD. Using quantitative real-time polymerase chain reaction, we show the maternally inherited FOXP2 to be comparatively underexpressed. Our results indicate that absence of paternal FOXP2 is the cause of DVD in patients with SRS with maternal UPD7. The data also point to a role for differential parent-of-origin expression of FOXP2 in human speech development.
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.forename: Aino
authors.initials: A
authors.lastname: Kalervo
authors.forename: Marita
authors.initials: M
authors.lastname: Lipsanen-Nyman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Skaug
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakabayashi
authors.forename: Brenda
authors.initials: B
authors.lastname: Finucane
authors.forename: Danielle
authors.initials: D
authors.lastname: Hartung
authors.forename: Micheil
authors.initials: M
authors.lastname: Innes
authors.forename: Batsheva
authors.initials: B
authors.lastname: Kerem
authors.forename: Malgorzata J
authors.initials: MJ
authors.lastname: Nowaczyk
authors.forename: Joseph
authors.initials: J
authors.lastname: Rivlin
authors.forename: Wendy
authors.initials: W
authors.lastname: Roberts
authors.forename: Lili
authors.initials: L
authors.lastname: Senman
authors.forename: Anne
authors.initials: A
authors.lastname: Summers
authors.forename: Peter
authors.initials: P
authors.lastname: Szatmari
authors.forename: Virginia
authors.initials: V
authors.lastname: Wong
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
authors.forename: Susan
authors.initials: S
authors.lastname: Zeesman
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Osborne
authors.forename: Janis Oram
authors.initials: JO
authors.lastname: Cardy
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Katariina
authors.initials: K
authors.lastname: Hannula-Jouppi
mesh_terms: D001072:Apraxias / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics; D002460:Cell Line; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D018392:Genomic Imprinting; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013577:Syndrome; D014178:Translocation, Genetic; D024182:Uniparental Disomy
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors