User:Osaobento/sandbox

Clinical Significance
The FOXP2 gene has been implicated in several cognitive functions including; general brain development, language, and synaptic plasticity. The FOXP2 gene region acts as a transcription factor for the forkhead box P2 protein. Transcription factors affect other regions, and the forkhead box P2 protein has been suggested to also act as a transcription factor for hundreds of genes. This prolific involvement opens the possibility that the FOXP2 gene is much more extensive than originally thought. Other targets of transcription have been researched without correlation to FOXP2. Specifically, FOXP2 has been investigated in correlation with autism and dyslexia, however with no mutation was discovered as the cause. One well identified target is language. Although some research disagrees with this correlation the majority of research shows that a mutated FOXP2 causes the observed production deficiency.

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) or Childhood Apraxia of Speech (CAS) So far this type of mutation has only been discovered in three families across the world including the original KE family. A missense mutation causing an arginine-to-histidine substitution (R553H) in the DNA-binding domain is thought to be the abnormality in KE. 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.

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. 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. It is believed that a major part of this speech deficit comes from an inability to coordinate of the movements necessary to produce normal speech including mouth and tongue shaping. Additionally, there are more general impairments with the processing of the grammatical and linguistic aspects of speech. 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. Clinically these patients can also have difficulty coughing, sneezing, and/or clearing their throats.