Skip to main content
SpringerLink
Log in

Genetic Pathways Implicated in Speech and Language

  • Chapter
  • First Online:
Animal Models of Speech and Language Disorders

Abstract

Disorders of speech and language are highly heritable, providing strong support for a genetic basis. However, the underlying genetic architecture is complex, involving multiple risk factors. This chapter begins by discussing genetic loci associated with common multifactorial language-related impairments and goes on to detail the only gene (known as FOXP2) to be directly implicated in a rare monogenic speech and language disorder. Although FOXP2 was initially uncovered in humans, model systems have been invaluable in progressing our understanding of the function of this gene and its associated pathways in language-related areas of the brain. Research in species from mouse to songbird has revealed effects of this gene on relevant behaviours including acquisition of motor skills and learned vocalisations and demonstrated a role for Foxp2 in neuronal connectivity and signalling, particularly in the striatum. Animal models have also facilitated the identification of wider neurogenetic networks thought to be involved in language development and disorder and allowed the investigation of new candidate genes for disorders involving language, such as CNTNAP2 and FOXP1. Ongoing work in animal models promises to yield new insights into the genetic and neural mechanisms underlying human speech and language.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Neils J, Aram DM (1986) Family history of children with developmental language disorders. Percept Mot Skills 63(2 Pt 1):655–658

    PubMed  CAS  Google Scholar 

  2. Lewis BA, Ekelman BL, Aram DM (1989) A familial study of severe phonological disorders. J Speech Hear Res 32(4):713–724

    PubMed  CAS  Google Scholar 

  3. Tallal P, Ross R, Curtiss S (1989) Familial aggregation in specific language impairment. J Speech Hear Disord 54(2):167–173

    PubMed  CAS  Google Scholar 

  4. Tomblin JB (1989) Familial concentration of developmental language impairment. J Speech Hear Disord 54(2):287–295

    PubMed  CAS  Google Scholar 

  5. Felsenfeld S, Plomin R (1997) Epidemiological and offspring analyses of developmental speech disorders using data from the Colorado Adoption Project. J Speech Lang Hear Res 40(4):778–791

    PubMed  CAS  Google Scholar 

  6. Lewis BA, Thompson LA (1992) A study of developmental speech and language disorders in twins. J Speech Hear Res 35(5):1086–1094

    PubMed  CAS  Google Scholar 

  7. Bishop DV, North T, Donlan C (1995) Genetic basis of specific language impairment: evidence from a twin study. Dev Med Child Neurol 37(1):56–71

    PubMed  CAS  Google Scholar 

  8. Tomblin JB, Buckwalter PR (1998) Heritability of poor language achievement among twins. J Speech Lang Hear Res 41(1):188–199

    PubMed  CAS  Google Scholar 

  9. Hayiou-Thomas ME, Dale PS, Plomin R (2012) The etiology of variation in language skills changes with development: a longitudinal twin study of language from 2 to 12 years. Dev Sci 15(2):233–249

    PubMed  Google Scholar 

  10. Kovas Y, Hayiou-Thomas ME, Oliver B et al (2005) Genetic influences in different aspects of language development: the etiology of language skills in 4.5-year-old twins. Child Dev 76(3):632–651

    PubMed  Google Scholar 

  11. Hoekstra R, Bartels M, Boomsma D (2007) Longitudinal genetic study of verbal and nonverbal IQ from early childhood to young adulthood. Learn Individ Diff 17(2):97–114

    Google Scholar 

  12. Stromswold K (2001) The heritability of language: a review and metaanalysis of twin, adoption, and linkage studies. Language 77(4):647–723

    Google Scholar 

  13. Fisher SE, Lai CSL, Monaco AP (2003) Deciphering the genetic basis of speech and language disorders. Annu Rev Neurosci 26:57–80

    PubMed  CAS  Google Scholar 

  14. Bartlett CW, Flax JF, Logue MW et al (2002) A major susceptibility locus for specific language impairment is located on 13q21. Am J Hum Genet 71(1):45–55

    PubMed  CAS  Google Scholar 

  15. Tomblin JB, Records NL, Buckwalter P et al (1997) Prevalence of specific language impairment in kindergarten children. J Speech Lang Hear Res 40(6):1245–1260

    PubMed  CAS  Google Scholar 

  16. The SLI Consortium (2002) A genomewide scan identifies two novel loci involved in specific language impairment. Am J Hum Genet 70(2):384–398

    Google Scholar 

  17. The SLI Consortium (SLIC) (2004) Highly significant linkage to the SLI1 locus in an expanded sample of individuals affected by specific language impairment. Am J Hum Genet 74(6):1225–1238

    Google Scholar 

  18. Newbury DF, Winchester L, Addis L et al (2009) CMIP and ATP2C2 modulate phonological short-term memory in language impairment. Am J Hum Genet 85(2):264–272

    PubMed  CAS  Google Scholar 

  19. Bartlett CW, Flax JF, Logue MW et al (2004) Examination of potential overlap in autism and language loci on chromosomes 2, 7, and 13 in two independent samples ascertained for specific language impairment. Hum Hered 57(1):10–20

    PubMed  Google Scholar 

  20. Poelmans G, Buitelaar JK, Pauls DL, Franke B (2011) A theoretical molecular network for dyslexia: integrating available genetic findings. Mol Psychiatry 16(4):365–382

    PubMed  CAS  Google Scholar 

  21. Scerri TS, Schulte-Körne G (2010) Genetics of developmental dyslexia. Eur Child Adolesc Psychiatry 19(3):179–197

    PubMed  Google Scholar 

  22. Abrahams BS, Geschwind DH (2010) Connecting genes to brain in the autism spectrum disorders. Arch Neurol 67(4):395–399

    PubMed  Google Scholar 

  23. Holt R, Monaco AP (2011) Links between genetics and pathophysiology in the autism spectrum disorders. EMBO Mol Med 3(8):438–450

    PubMed  CAS  Google Scholar 

  24. El-Fishawy P, State MW (2010) The genetics of autism: key issues, recent findings, and clinical implications. Psychiatr Clin North Am 33(1):83–105

    PubMed  Google Scholar 

  25. Hurst JA, Baraitser M, Auger E, Graham F, Norell S (1990) An extended family with a dominantly inherited speech disorder. Dev Med Child Neurol 32(4):352–355

    PubMed  CAS  Google Scholar 

  26. Fisher SE, Vargha-Khadem F, Watkins KEE et al (1998) Localisation of a gene implicated in a severe speech and language disorder. Nat Genet 18(2):168–170

    PubMed  CAS  Google Scholar 

  27. Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP (2001) A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413(6855):519–523

    PubMed  CAS  Google Scholar 

  28. Vargha-Khadem F, Watkins K, Alcock K, Fletcher P, Passingham R (1995) Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. Proc Natl Acad Sci U S A 92(3):930–933

    PubMed  CAS  Google Scholar 

  29. Gopnik M (1990) Feature-blind grammar and dysphagia. Nature 344(6268):715

    PubMed  CAS  Google Scholar 

  30. Watkins KE, Dronkers NF, Vargha-Khadem F (2002) Behavioural analysis of an inherited speech and language disorder: comparison with acquired aphasia. Brain 125(Pt 3):452–464

    PubMed  CAS  Google Scholar 

  31. Vargha-Khadem F, Watkins KE, Price CJ et al (1998) Neural basis of an inherited speech and language disorder. Proc Natl Acad Sci U S A 95(21):12695–12700

    PubMed  CAS  Google Scholar 

  32. Alcock KJ, Passingham RE, Watkins KE, Vargha-Khadem F (2000) Oral dyspraxia in inherited speech and language impairment and acquired dysphasia. Brain Lang 75(1):17–33

    PubMed  CAS  Google Scholar 

  33. Alcock KJ, Wade D, Anslow P, Passingham RE (2000) Pitch and timing abilities in adult left-hemisphere-dysphasic and right-hemisphere-damaged subjects. Brain Lang 75(1):47–65

    PubMed  CAS  Google Scholar 

  34. Tallal P, Sainburg RL, Jernigan T (1991) The neuropathology of developmental dysphasia: behavioral, morphological, and physiological evidence for a pervasive temporal processing disorder. Read Writ 3(3–4):363–377

    PubMed  Google Scholar 

  35. Belton E, Salmond CH, Watkins KE, Vargha-Khadem F, Gadian DG (2003) Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia. Hum Brain Mapp 18(3):194–200

    PubMed  Google Scholar 

  36. Liegeois F, Baldeweg T, Connelly A et al (2003) Language fMRI abnormalities associated with FOXP2 gene mutation. Nat Neurosci 6(11):1230–1237

    PubMed  CAS  Google Scholar 

  37. Weigel D, Jurgens G, Kuttner F, Seifert E, Jackle H (1989) The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. Cell 57(4):645–658

    PubMed  CAS  Google Scholar 

  38. Clark KL, Halay ED, Lai E, Burley SK (1993) Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature 364(6436):412–420

    PubMed  CAS  Google Scholar 

  39. Overdier DG, Porcella A, Costa RH (1994) The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol Cell Biol 14(4):2755–2766

    PubMed  CAS  Google Scholar 

  40. Pierrou S, Hellqvist M, Samuelsson L, Enerback S, Carlsson P (1994) Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending. EMBO J 13(20):5002–5012

    PubMed  CAS  Google Scholar 

  41. Kaufmann E, Hoch M, Jackle H (1994) The interaction of DNA with the DNA-binding domain encoded by the Drosophila gene fork head. Eur J Biochem 223(2):329–337

    PubMed  CAS  Google Scholar 

  42. Wang B, Lin D, Li C, Tucker P (2003) Multiple domains define the expression and regulatory properties of Foxp1 forkhead transcriptional repressors. J Biol Chem 278(27):24259–24268

    PubMed  CAS  Google Scholar 

  43. Vernes SC, Nicod J, Elahi FM et al (2006) Functional genetic analysis of mutations implicated in a human speech and language disorder. Hum Mol Genet 15(21):3154–3167

    PubMed  CAS  Google Scholar 

  44. Katoh M, Katoh M (2004) Human FOX gene family (Review). Int J Oncol 25(5):1495–1500

    PubMed  CAS  Google Scholar 

  45. Kaestner KH, Knochel W, Martinez DE (2000) Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev 14(2):142–146

    PubMed  CAS  Google Scholar 

  46. Shu W, Yang H, Zhang L, Lu MM, Morrisey EE (2001) Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors. J Biol Chem 276(29):27488–27497

    PubMed  CAS  Google Scholar 

  47. Lu MM, Li S, Yang H, Morrisey EE, Min M (2002) Foxp4: a novel member of the Foxp subfamily of winged-helix genes co-expressed with Foxp1 and Foxp2 in pulmonary and gut tissues. Gene Expr Patterns 2(3–4):223–228

    PubMed  CAS  Google Scholar 

  48. Li S, Weidenfeld J, Morrisey EE (2004) Transcriptional and DNA binding activity of the Foxp1/2/4 family is modulated by heterotypic and homotypic protein interactions. Mol Cell Biol 24(2):809–822

    PubMed  CAS  Google Scholar 

  49. Ferland RJ, Cherry TJ, Preware PO, Morrisey EE, Walsh CA (2003) Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J Comp Neurol 460(2):266–279

    PubMed  CAS  Google Scholar 

  50. Lai CSL, Gerrelli D, Monaco AP, Fisher SE, Copp AJ (2003) FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder. Brain 126(Pt 11):2455–2462

    PubMed  Google Scholar 

  51. Takahashi K, Liu F-C, Hirokawa K, Takahashi H (2008) Expression of Foxp4 in the developing and adult rat forebrain. J Neurosci Res 86(14):3106–3116

    PubMed  CAS  Google Scholar 

  52. Tam WY, Leung CKY, Tong KK, Kwan KM (2011) Foxp4 is essential in maintenance of Purkinje cell dendritic arborization in the mouse cerebellum. Neuroscience 172:562–571

    PubMed  CAS  Google Scholar 

  53. Campbell AJ, Lyne L, Brown PJ et al (2010) Aberrant expression of the neuronal transcription factor FOXP2 in neoplastic plasma cells. Br J Haematol 149(2):221–230

    PubMed  CAS  Google Scholar 

  54. Banham AH, Beasley N, Campo E et al (2001) The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res 61(24):8820–8829

    PubMed  CAS  Google Scholar 

  55. Dasen JS, De Camilli A, Wang B, Tucker PW, Jessell TM (2008) Hox repertoires for motor neuron diversity and connectivity gated by a single accessory factor, FoxP1. Cell 134(2):304–316

    PubMed  CAS  Google Scholar 

  56. Rousso DL, Gaber ZB, Wellik D, Morrisey EE, Novitch BG (2008) Coordinated actions of the forkhead protein Foxp1 and Hox proteins in the columnar organization of spinal motor neurons. Neuron 59(2):226–240

    PubMed  CAS  Google Scholar 

  57. Shu W, Lu MM, Zhang Y et al (2007) Foxp2 and Foxp1 cooperatively regulate lung and esophagus development. Development 134(10):1991–2000

    PubMed  CAS  Google Scholar 

  58. Li S, Zhou D, Lu MM, Morrisey EE (2004) Advanced cardiac morphogenesis does not require heart tube fusion. Science 305(5690):1619–1622

    PubMed  CAS  Google Scholar 

  59. Wang B, Weidenfeld J, Lu MM et al (2004) Foxp1 regulates cardiac outflow tract, endocardial cushion morphogenesis and myocyte proliferation and maturation. Development 131(18):4477–4487

    PubMed  CAS  Google Scholar 

  60. Wildin RS, Ramsdell F, Faravelli F et al (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 (Brief Communications). Group 27:20–21

    Google Scholar 

  61. MacDermot KD, Bonora E, Sykes N et al (2005) Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits. Am J Hum Genet 76(6):1074–1080

    PubMed  CAS  Google Scholar 

  62. Shriberg LD, Ballard KJ, Tomblin JB et al (2006) Speech, prosody, and voice characteristics of a mother and daughter with a 7;13 translocation affecting FOXP2. J Speech Lang Hear Res 49(3):500–525

    PubMed  Google Scholar 

  63. Tomblin JB, O’Brien M, Shriberg LD et al (2009) Language features in a mother and daughter of a chromosome 7;13 translocation involving FOXP2. J Speech Lang Hear Res 52(5):1157–1174

    PubMed  Google Scholar 

  64. Kosho T, Sakazume S, Kawame H et al (2007) De-novo balanced translocation between 7q31 and 10p14 in a girl with central precocious puberty, moderate mental retardation, and severe speech impairment. Clin Dysmorphol 17(1):31–34

    Google Scholar 

  65. Feuk L, Kalervo A, Lipsanen-Nyman M et al (2006) Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia. Am J Hum Genet 79(5):965–972

    PubMed  CAS  Google Scholar 

  66. Zeesman S, Nowaczyk MJM, Teshima I et al (2006) Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2. Am J Med Genet A 140(5):509–514

    PubMed  Google Scholar 

  67. Lennon PA, Cooper ML, Peiffer DA et al (2007) Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review. Am J Med Genet A 143(8):791–798

    Google Scholar 

  68. Zilina O, Reimand T, Zjablovskaja P et al (2012) Maternally and paternally inherited deletion of 7q31 involving the FOXP2 gene in two families. Am J Med Genet A 158A(1):254–256

    PubMed  CAS  Google Scholar 

  69. Rice GM, Raca G, Jakielski KJ et al (2012) Phenotype of FOXP2 haploinsufficiency in a mother and son. Am J Med Genet A 158A(1):174–181

    PubMed  Google Scholar 

  70. Palka C, Alfonsi M, Mohn A et al (2012) Mosaic 7q31 deletion involving FOXP2 gene associated with language impairment. Pediatrics 129(1):e183–e188

    PubMed  Google Scholar 

  71. Enard W, Przeworski M, Fisher SE et al (2002) Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418(6900):869–872

    PubMed  CAS  Google Scholar 

  72. Zhang J, Webb DM, Podlaha O (2002) Accelerated protein evolution and origins of human-specific features: Foxp2 as an example. Genetics 162(4):1825–1835

    PubMed  CAS  Google Scholar 

  73. Itakura T, Chandra A, Yang Z et al (2008) The medaka FoxP2, a homologue of human language gene FOXP2, has a diverged structure and function. J Biochem 143(3):407–416

    PubMed  CAS  Google Scholar 

  74. Santos ME, Athanasiadis A, Leitão AB, DuPasquier L, Sucena E (2011) Alternative splicing and gene duplication in the evolution of the FoxP gene subfamily. Mol Biol Evol 28(1):237–247

    PubMed  CAS  Google Scholar 

  75. Fisher SE, Marcus GF (2006) The eloquent ape: genes, brains and the evolution of language. Nat Rev Genet 7:9–20

    PubMed  CAS  Google Scholar 

  76. Fisher SE, Scharff C (2009) FOXP2 as a molecular window into speech and language. Trends Genet 25(4):166–177

    PubMed  CAS  Google Scholar 

  77. Groszer M, Keays DA, Deacon RMJ et al (2008) Impaired synaptic plasticity and motor learning in mice with a point mutation implicated in human speech deficits. Curr Biol 18(5):354–362

    PubMed  CAS  Google Scholar 

  78. French CA, Jin X, Campbell TG, et al. An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning. Mol Psychiatry 2011. doi:10.1038/mp:1-9

  79. Kurt S, Groszer M, Fisher SE, Ehret G (2009) Modified sound-evoked brainstem potentials in Foxp2 mutant mice. Brain Res 1289:30–36

    PubMed  CAS  Google Scholar 

  80. Shu W, Cho JY, Jiang Y et al (2005) Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc Natl Acad Sci U S A 102(27):9643–9648

    PubMed  CAS  Google Scholar 

  81. Fujita E, Tanabe Y, Shiota A et al (2008) Ultrasonic vocalization impairment of Foxp2 (R552H) knockin mice related to speech-language disorder and abnormality of Purkinje cells. Proc Natl Acad Sci U S A 105(8):3117–3122

    PubMed  CAS  Google Scholar 

  82. Gaub S, Groszer M, Fisher SE, Ehret G (2010) The structure of innate vocalizations in Foxp2-deficient mouse pups. Genes Brain Behav 9(4):390–401

    PubMed  CAS  Google Scholar 

  83. Jürgens U (2009) The neural control of vocalization in mammals: a review. J Voice 23(1):1–10

    PubMed  Google Scholar 

  84. Enard W, Gehre S, Hammerschmidt K et al (2009) A humanized version of Foxp2 affects cortico-basal ganglia circuits in mice. Cell 137(5):961–971

    PubMed  CAS  Google Scholar 

  85. Webb DM, Zhang J (2005) FoxP2 in song-learning birds and vocal-learning mammals. J Hered 96(3):212–216

    PubMed  CAS  Google Scholar 

  86. Enard W (2011) FOXP2 and the role of cortico-basal ganglia circuits in speech and language evolution. Curr Opin Neurobiol 21(3):415–424

    PubMed  CAS  Google Scholar 

  87. Reimers-Kipping S, Hevers W, Pääbo S, Enard W, Paabo S (2011) Humanized Foxp2 specifically affects cortico-basal ganglia circuits. Neuroscience 175:75–84

    PubMed  CAS  Google Scholar 

  88. Haesler S, Rochefort C, Georgi B et al (2007) Incomplete and inaccurate vocal imitation after knockdown of FoxP2 in songbird basal ganglia nucleus Area X. PLoS Biol 5(12):e321

    PubMed  Google Scholar 

  89. French CA, Groszer M, Preece C et al (2007) Generation of mice with a conditional Foxp2 null allele. Genesis 45(7):440–446

    PubMed  CAS  Google Scholar 

  90. Vernes SC, Spiteri E, Nicod J et al (2007) High-throughput analysis of promoter occupancy reveals direct neural targets of FOXP2, a gene mutated in speech and language disorders. Am J Hum Genet 81(6):1232–1250

    PubMed  CAS  Google Scholar 

  91. Spiteri E, Konopka G, Coppola G et al (2007) Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain. Am J Hum Genet 81(6):1144–1157

    PubMed  CAS  Google Scholar 

  92. Roll P, Vernes SC, Bruneau N et al (2010) Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex. Hum Mol Genet 19(24):4848–4860

    PubMed  CAS  Google Scholar 

  93. Vernes SC, Oliver PL, Spiteri E et al (2011) Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain. PLoS Genet 7(7):e1002145

    PubMed  CAS  Google Scholar 

  94. Chen K, Rajewsky N (2007) The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8(2):93–103

    PubMed  CAS  Google Scholar 

  95. Vernes SC, Newbury DF, Abrahams BS et al (2008) A functional genetic link between distinct developmental language disorders. N Eng J Med 359(22):2337–2345

    CAS  Google Scholar 

  96. Poliak S, Salomon D, Elhanany H et al (2003) Juxtaparanodal clustering of Shaker-like K + channels in myelinated axons depends on Caspr2 and TAG-1. J Cell Biol 162(6):1149–1160

    PubMed  CAS  Google Scholar 

  97. Traka M, Goutebroze L, Denisenko N et al (2003) Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers. J Cell Biol 162(6):1161–1172

    PubMed  CAS  Google Scholar 

  98. Arking DE, Cutler DJ, Brune CW et al (2008) A common genetic variant in the neurexin superfamily member CNTNAP2 increases familial risk of autism. Am J Hum Genet 82(1):160–164

    PubMed  CAS  Google Scholar 

  99. Verkerk AJ, Mathews CA, Joosse M et al (2003) CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics 82(1):1–9

    PubMed  CAS  Google Scholar 

  100. Alarcon M, Abrahams BS, Stone JL et al (2008) Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 82(1):150–159

    PubMed  CAS  Google Scholar 

  101. Strauss KA, Puffenberger EG, Huentelman MJ et al (2006) Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2. N Engl J Med 354(13):1370–1377

    PubMed  CAS  Google Scholar 

  102. Rasband MN (2004) It’s “juxta” potassium channel! J Neurosci Res 76(6):749–757

    PubMed  CAS  Google Scholar 

  103. Abrahams BS, Tentler D, Perederiy JV et al (2007) Genome-wide analyses of human perisylvian cerebral cortical patterning. Proc Natl Acad Sci U S A 104(45):17849–17854

    PubMed  CAS  Google Scholar 

  104. Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA (2004) Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction. J Neurosci 24(13):3152–3163

    PubMed  CAS  Google Scholar 

  105. Vernes SC, MacDermot KD, Monaco AP, Fisher SE (2009) Assessing the impact of FOXP1 mutations on developmental verbal dyspraxia. Eur J Hum Genet 17(10):1354–1358

    PubMed  CAS  Google Scholar 

  106. Pariani MJ, Spencer A, Graham JM, Rimoin DL (2009) A 785kb deletion of 3p14.1p13, including the FOXP1 gene, associated with speech delay, contractures, hypertonia and blepharophimosis. Eur J Med Genet 52(2–3):123–127

    PubMed  Google Scholar 

  107. Carr CW, Moreno-De-Luca D, Parker C et al (2010) Chiari I malformation, delayed gross motor skills, severe speech delay, and epileptiform discharges in a child with FOXP1 haploinsufficiency. Eur J Hum Genet 18(11):1216–1220

    PubMed  CAS  Google Scholar 

  108. Palmesino E, Rousso DL, Kao T-J et al (2010) Foxp1 and lhx1 coordinate motor neuron migration with axon trajectory choice by gating Reelin signalling. PLoS Biol 8(8):e1000446

    PubMed  Google Scholar 

  109. Hamdan FF, Daoud H, Rochefort D et al (2010) De novo mutations in FOXP1 in cases with intellectual disability, autism, and language impairment. Am J Hum Genet 87(5):671–678

    PubMed  CAS  Google Scholar 

  110. Horn D, Kapeller J, Rivera-Brugués N et al (2010) Identification of FOXP1 deletions in three unrelated patients with mental retardation and significant speech and language deficits. Hum Mutat 31(11):E1851–E1860

    PubMed  CAS  Google Scholar 

  111. O’Roak BJ, Deriziotis P, Lee C et al (2011) Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet 43(6):585–589

    PubMed  Google Scholar 

  112. Konopka G, Bomar JM, Winden K et al (2009) Human-specific transcriptional regulation of CNS development genes by FOXP2. Nature 462(7270):213–217

    PubMed  CAS  Google Scholar 

  113. Hilliard AT, Miller JE, Fraley ER, Horvath S, White SA (2012) Molecular microcircuitry underlies functional specification in a basal ganglia circuit dedicated to vocal learning. Neuron 73(3):537–552

    PubMed  CAS  Google Scholar 

  114. French CA, Jin X, Campbell TG, Gerfen E, Groszer M, Fisher SE, Costa RM (2012) An aetiological Foxp2 mutation causes aberrant striatal activity and alters plasticity during skill learning. Mol Psychiatry 17(11):1077–1085

    PubMed  CAS  Google Scholar 

  115. Rein ML, Deussing JM (2012) The optogenetic (r)evolution. Mol Genet Genomics 287(2):95–109

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Max Planck Institute for Psycholinquistics, Wundtlaan 1, Nijmegen, 6525 XD, The Netherlands

    Sonja C. Vernes D.Phil. & Simon E. Fisher D.Phil.

Authors
  1. Sonja C. Vernes D.Phil.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon E. Fisher D.Phil.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sonja C. Vernes D.Phil. .

Editor information

Editors and Affiliations

  1. Department of Neurology, Methodist Hospital Research Institute, Houston, Texas, USA

    Santosh A. Helekar

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Vernes, S.C., Fisher, S.E. (2013). Genetic Pathways Implicated in Speech and Language. In: Helekar, S. (eds) Animal Models of Speech and Language Disorders. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8400-4_2

Download citation

Publish with us

Policies and ethics

Search

Navigation