title: Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits.
abstract: Mental retardation affects 2-3% of the population and shows a high heritability.Neurodevelopmental disorders that include pronounced impairment in language and speech skills occur less frequently. For most cases, the molecular basis of mental retardation with or without speech and language disorder is unknown due to the heterogeneity of underlying genetic factors.We have used molecular karyotyping on 1523 patients with mental retardation to detect copy number variations (CNVs) including deletions or duplications. These studies revealed three heterozygous overlapping deletions solely affecting the forkhead box P1 (FOXP1) gene. All three patients had moderate mental retardation and significant language and speech deficits. Since our results are consistent with a de novo occurrence of these deletions, we considered them as causal although we detected a single large deletion including FOXP1 and additional genes in 4104 ancestrally matched controls. These findings are of interest with regard to the structural and functional relationship between FOXP1 and FOXP2. Mutations in FOXP2 have been previously related to monogenic cases of developmental verbal dyspraxia. Both FOXP1 and FOXP2 are expressed in songbird and human brain regions that are important for the developmental processes that culminate in speech and language.
authors.affiliation: Institute of Medical Genetics, Charité, University Medicine of Berlin, Berlin, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.forename: Johannes
authors.initials: J
authors.lastname: Kapeller
authors.forename: Núria
authors.initials: N
authors.lastname: Rivera-Brugués
authors.forename: Ute
authors.initials: U
authors.lastname: Moog
authors.forename: Bettina
authors.initials: B
authors.lastname: Lorenz-Depiereux
authors.forename: Sebastian
authors.initials: S
authors.lastname: Eck
authors.forename: Maja
authors.initials: M
authors.lastname: Hempel
authors.forename: Janine
authors.initials: J
authors.lastname: Wagenstaller
authors.forename: Alex
authors.initials: A
authors.lastname: Gawthrope
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Monaco
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Eva
authors.initials: E
authors.lastname: Wohlleber
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Connie R
authors.initials: CR
authors.lastname: Bezzina
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Stephanie
authors.initials: S
authors.lastname: Spranger
authors.forename: Pablo
authors.initials: P
authors.lastname: Villavicencio-Lorini
authors.forename: Wenke
authors.initials: W
authors.lastname: Seifert
authors.forename: Jochen
authors.initials: J
authors.lastname: Rosenfeld
authors.forename: Eva
authors.initials: E
authors.lastname: Klopocki
authors.forename: Gudrun A
authors.initials: GA
authors.lastname: Rappold
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D053960:DNA Breaks; D017931:DNA Primers / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics*; D007806:Language Disorders / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D013064:Speech Disorders / Q000235:genetics*
chemical_list: D017931:DNA Primers; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins