title: FOXP2 variants in 14 individuals with developmental speech and language disorders broaden the mutational and clinical spectrum.
abstract: Disruptions of the FOXP2 gene, encoding a forkhead transcription factor, are the first known monogenic cause of a speech and language disorder. So far, mainly chromosomal rearrangements such as translocations or larger deletions affecting FOXP2 have been reported. Intragenic deletions or convincingly pathogenic point mutations in FOXP2 have up to date only been reported in three families. We thus aimed at a further characterisation of the mutational and clinical spectrum.
  
  
  
  Chromosomal microarray testing, trio exome sequencing, multigene panel sequencing and targeted sequencing of FOXP2 were performed in individuals with variable developmental disorders, and speech and language deficits.
  
  
  
  We identified four different truncating mutations, two novel missense mutations within the forkhead domain and an intragenic deletion in FOXP2 in 14 individuals from eight unrelated families. Mutations occurred de novo in four families and were inherited from an affected parent in the other four. All index patients presented with various manifestations of language and speech impairment. Apart from two individuals with normal onset of speech, age of first words was between 4 and 7 years. Articulation difficulties such as slurred speech, dyspraxia, stuttering and poor pronunciation were frequently noted. Motor development was normal or only mildly delayed. Mild cognitive impairment was reported for most individuals.
  
  
  
  By identifying intragenic deletions or mutations in 14 individuals from eight unrelated families with variable developmental delay/cognitive impairment and speech and language deficits, we considerably broaden the mutational and clinical spectrum associated with aberrations in FOXP2.
authors: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors: Miriam S
authors: MS
authors: Reuter
authors: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
authors: Angelika
authors: A
authors: Riess
authors: Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
authors: Ute
authors: U
authors: Moog
authors: Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.|Faculty of Medical and Human Sciences, Institute of Human Development, University of Manchester, Manchester, UK.
authors: Tracy A
authors: TA
authors: Briggs
authors: Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: Kate E
authors: KE
authors: Chandler
authors: Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland.
authors: Anita
authors: A
authors: Rauch
authors: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
authors: Miriam
authors: M
authors: Stampfer
authors: Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland.
authors: Katharina
authors: K
authors: Steindl
authors: Genetikum, Neu-Ulm, Germany.
authors: Dieter
authors: D
authors: Gläser
authors: Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland.
authors: Pascal
authors: P
authors: Joset
authors: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors: Mandy
authors: M
authors: Krumbiegel
authors: Kinderzentrum St. Martin, Regensburg, Germany.
authors: Harald
authors: H
authors: Rabe
authors: Kinderzentrum St. Martin, Regensburg, Germany.
authors: Uta
authors: U
authors: Schulte-Mattler
authors: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
authors: Peter
authors: 0000-0001-9414-4555
authors: P
authors: Bauer
authors: Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.
authors: Stefanie
authors: S
authors: Beck-Wödl
authors: Centre for Human Genetics, Freiburg, Germany.
authors: Jürgen
authors: J
authors: Kohlhase
authors: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors: André
authors: A
authors: Reis
authors: Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors: Christiane
authors: C
authors: Zweier
mesh_terms: D002658:Developmental Disabilities / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007806:Language Disorders / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D013060:Speech / Q000502:physiology; D013064:Speech Disorders / Q000235:genetics*
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors
keywords: FOXP2; developmental delay; language; speech