Editing FOXP2 (section)

=== Language disorder ===
It is theorized that the translocation of the 7q31.2 region of the FOXP2 gene causes a severe language impairment called [[developmental verbal dyspraxia]] (DVD)<ref name="GHR_FOXP2_disorders"/> or childhood apraxia of speech (CAS)<ref>{{cite journal | vauthors = Morgan A, Fisher SE, Scheffer I, Hildebrand M | title = FOXP2-Related Speech and Language Disorders | journal = GenReviews | date = 23 June 2016 | pmid = 27336128 | publisher = University of Washington | veditors = Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ, Stephens K, Amemiya A }}</ref> So far this type of mutation has only been discovered in three families across the world including the original KE family.<ref name="Reuter_2017"/> A missense mutation causing an arginine-to-histidine substitution (R553H) in the DNA-binding domain is thought to be the abnormality in KE.<ref name="Preuss_2012" /> This would cause a normally basic residue to be fairly acidic and highly reactive at the body's pH. A heterozygous nonsense mutation, R328X variant, produces a truncated protein involved in speech and language difficulties in one KE individual and two of their close family members. R553H and R328X mutations also affected nuclear localization, DNA-binding, and the transactivation (increased gene expression) properties of FOXP2.<ref name="MacDermot_2005" />

These individuals present with deletions, translocations, and missense mutations. When tasked with repetition and verb generation, these individuals with DVD/CAS had decreased activation in the putamen and Broca's area in fMRI studies. These areas are commonly known as areas of language function.<ref>{{cite journal | vauthors = Vargha-Khadem F, Gadian DG, Copp A, Mishkin M | title = FOXP2 and the neuroanatomy of speech and language | journal = Nature Reviews. Neuroscience | volume = 6 | issue = 2 | pages = 131–8 | date = February 2005 | pmid = 15685218 | doi = 10.1038/nrn1605 | s2cid = 2504002 }}</ref> This is one of the primary reasons that FOXP2 is known as a language gene. They have delayed onset of speech, difficulty with articulation including slurred speech, stuttering, and poor pronunciation, as well as dyspraxia.<ref name="Reuter_2017"/> It is believed that a major part of this speech deficit comes from an inability to coordinate the movements necessary to produce normal speech including mouth and tongue shaping.<ref name="GHR_FOXP2_disorders" /> Additionally, there are more general impairments with the processing of the grammatical and linguistic aspects of speech.<ref name="MacDermot_2005" /> These findings suggest that the effects of FOXP2 are not limited to motor control, as they include comprehension among other cognitive language functions. General mild motor and cognitive deficits are noted across the board.<ref name="Lennon_2007"/> Clinically these patients can also have difficulty coughing, sneezing, or clearing their throats.<ref name="GHR_FOXP2_disorders" />

While FOXP2 has been proposed to play a critical role in the development of speech and language, this view has been challenged by the fact that the gene is also expressed in other mammals as well as birds and fish that do not speak.<ref>{{cite book | vauthors = Friederici AD | author-link = Angela D. Friederici | title = 'Language in the Brain | date = 2016 | publisher = The MIT Press | location = Cambridge, MA | isbn = 978-0-262-03692-4 | page = 222 }}</ref> It has also been proposed that the FOXP2 transcription-factor is not so much a hypothetical 'language gene' but rather part of a regulatory machinery related to externalization of speech.<ref>{{cite book | vauthors = Berwick RC, Chomsky N | date = 2016 | title = Why Only Us? | isbn = 978-0-262-53349-2 | publisher = The MIT Press | location = Cambridge, MA | page = 76 }}</ref>