title: Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2.
abstract: BACKGROUND
  We report on a young female, who presents with a severe speech and language disorder and a balanced de novo complex chromosomal rearrangement, likely to have resulted from a chromosome 7 pericentromeric inversion, followed by a chromosome 7 and 11 translocation.
  
  
  RESULTS
  Using molecular cytogenetics, we mapped the four breakpoints to 7p21.1-15.3 (chromosome position: 20,954,043-21,001,537, hg19), 7q31 (chromosome position: 114,528,369-114,556,605, hg19), 7q21.3 (chromosome position: 93,884,065-93,933,453, hg19) and 11p12 (chromosome position: 38,601,145-38,621,572, hg19). These regions contain only non-coding transcripts (ENSG00000232790 on 7p21.1 and TCONS_00013886, TCONS_00013887, TCONS_00014353, TCONS_00013888 on 7q21) indicating that no coding sequences are directly disrupted. The breakpoint on 7q31 mapped 200 kb downstream of FOXP2, a well-known language gene. No splice site or non-synonymous coding variants were found in the FOXP2 coding sequence. We were unable to detect any changes in the expression level of FOXP2 in fibroblast cells derived from the proband, although this may be the result of the low expression level of FOXP2 in these cells.
  
  
  CONCLUSIONS
  We conclude that the phenotype observed in this patient either arises from a subtle change in FOXP2 regulation due to the disruption of a downstream element controlling its expression, or from the direct disruption of non-coding RNAs.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford, OX3 7BN UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Moralli
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford, OX3 7BN UK.
authors.forename: Ron
authors.initials: R
authors.lastname: Nudel
authors.affiliation: Faculty of Linguistics, Philology and Phonetics, University of Oxford, Walton Street, Oxford, OX1 2HG UK ; Worcester College, University of Oxford, Oxford, OX1 2HB, UK.
authors.forename: May T M
authors.initials: MT
authors.lastname: Chan
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford, OX3 7BN UK.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Green
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford, OX3 7BN UK ; Department of Biomedical Sciences, University of Westminster, 115 New Cavendish Street, London, W1W 6UW UK.
authors.forename: Emanuela V
authors.initials: EV
authors.lastname: Volpi
authors.affiliation: Faculty of Modern languages, University of Oxford, 47 Wellington Square, Oxford, OX1 2JF UK ; Department of Spanish Philology and its Didactics, University of Huelva, Huelva, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Benítez-Burraco
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Headington, Oxford, OX3 7BN UK.
authors.forename: Dianne F
authors.initials: DF
authors.lastname: Newbury
authors.affiliation: Faculty of Linguistics, Philology and Phonetics, University of Oxford, Walton Street, Oxford, OX1 2HG UK ; Faculty of Modern languages, University of Oxford, 47 Wellington Square, Oxford, OX1 2JF UK.
authors.forename: Paloma
authors.initials: P
authors.lastname: García-Bellido
keywords: Chromosomal rearrangement; FOXP2 regulation; Language impairment; Non-coding elements; Spanish