FOXP2 and the neuroanatomy of speech and language

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作者
Faraneh Vargha-Khadem
David G. Gadian
Andrew Copp
Mortimer Mishkin
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[1] Institute of Child Health,
[2] University College London and Great Ormond Street Hospital for Children,undefined
[3] Laboratory of Neuropsychology,undefined
[4] National Institute of Mental Health,undefined
[5] Building 49,undefined
[6] Suite 1B-80,undefined
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Familial disorders of speech and language provided early evidence that genetic mutations could impair these abilities, but a causative mutation in a single gene was only recently identified. Mutations in FOXP2 cause an inherited verbal dyspraxia associated with an orofacial movement disorder in a family known by the label KE.Although the behavioural phenotype has been carefully studied, it is still unclear whether all the effects of the mutation are caused by a single core deficit in orofacial movement, or whether there are additional core deficits that can account for the grammatical, semantic and cognitive impairments that are found in affected family members.MRI scans of affected individuals showed no obvious focal abnormalities on conventional neuroradiological assesments, but more detailed analyses have revealed reductions in the volumes of several brain areas that are involved in motor functions, including the caudate nuclei, Broca's area, the precentral gyrus and the ventral cerebellum. Functional neuroimaging studies have also shown some abnormalities in patterns of activation.FOXP2 encodes a transcription factor that is expressed in the brain, lungs, heart and gut. In the brain, it is widely expressed in sensory, limbic and motor structures.The effects of a mutation in FOXP2, together with data on its expression, allow us to propose a model of FOXP2-dependent circuitry. We assume that the circuitry that underlies normal speech is similar to the frontostriatal and frontocerebellar circuits that modulate and control the motor cortex in the performance of other types of movement. Most of the areas in the proposed circuit express FOXP2, and several of these show abnormalities in affected members of the KE family.Much work is needed to clarify the details of the deficits caused by mutations in FOXP2 and to provide evidence that supports or contradicts our proposed circuitry. This work will involve behavioural, imaging, gene expression and gene knockout studies.
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页码:131 / 138
页数:7
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