FOXP2: novel exons, splice variants, and CAG repeat length stability

Hum Genet. 2002 Aug;111(2):136-44. doi: 10.1007/s00439-002-0768-5. Epub 2002 Jul 16.

Abstract

FOXP2 is a transcription factor containing a polyglutamine tract, a zinc-finger motif, and a forkhead DNA-binding domain. The FOXP2 gene is located on 7q31. A missense mutation in the forkhead domain (exon 14) and a balanced reciprocal translocation t(5;7)(q22;q31.2) with a breakpoint between exons 3b and 4 have recently been associated with a speech and language disorder (SPCH1). The role of FOXP2 in this neurodevelopmental disorder suggests that mutations in FOXP2 could cause other neuropsychiatric disorders. To begin investigation of this possibility, we examined the genomic structure and CAG/CAA repeat region of FOXP2. We detected little polymorphism and no expansions in the FOXP2 CAG/CAA repeat in 142 individuals with progressive movement disorders. We found evidence of alternate splice variants and six previously undetected exons: three 5' untranslated exons (s1, s2, s3), two additional untranslated exons (2a and 2b) between exons 2 and 3, a translated exon (4a) between exons 4 and 5, and a longer version of exon 10 (10+) that contains an alternate stop codon and produces a truncated protein (FOXP2-S). Our results suggest that FOXP2 spans at least 603 kb of genomic DNA, more than twice the previously defined region, and provide evidence of a promoter region flanking exon s1. This demonstration of additional FOXP2 exons and splice variants should facilitate understanding of FOXP2 function and the search for additional FOXP2 mutations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing / genetics*
  • Brain Chemistry
  • DNA Primers / chemistry
  • Exons / genetics*
  • Forkhead Transcription Factors
  • Genetic Variation
  • Humans
  • Introns
  • Molecular Sequence Data
  • Movement Disorders / genetics
  • Mutation / genetics
  • Peptide Fragments
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Trinucleotide Repeat Expansion / genetics*
  • Untranslated Regions / genetics

Substances

  • DNA Primers
  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • Peptide Fragments
  • RNA, Messenger
  • Transcription Factors
  • Untranslated Regions

Associated data

  • GENBANK/AF454830
  • GENBANK/AF467252
  • GENBANK/AF467253
  • GENBANK/AF467254
  • GENBANK/AF467255
  • GENBANK/AF467256
  • GENBANK/AF467257
  • GENBANK/AF467258
  • GENBANK/AF467259