 |
Faraneh Vargha-Khadem University College London Institute of Child Health and Great Ormond Street Hospital for Children London, UK |
From speech to gene:
FOXP2 and the KE family
Fifteen
of the 30 three-generational KE family members suffer from an orofacial
and verbal dyspraxia arising from an underlying impairment in the rapid
selection and accurate sequencing of orofacial movements most evident
in speech. Structural neuroimaging in the affected members revealed
bilateral abnormalities in a number of motor, and speech and
language-related brain regions. Functional
neuroimaging during verb generation and repetition tasks disclosed a
distinctly atypical pattern of activation (i.e. diffuse, bilateral, and
located predominantly in posterior cortical regions). Comparison
between affected and unaffected family members indicated that the FOXP2
mutation is associated with significant underactivation in several
regions that had been found to be morphologically abnormal, including
the inferior frontal gyrus. Together, these structural and functional
MR results provide a coherent explanation for the affected members'
striking and persistent disorder.
The neuropsychological and neuroimaging findings will be related to the genetic basis of the disorder in the KE family and to that of other cases with mutations and/or deletions of the FOXP2 gene, and to the pattern of gene expression during embryological development in humans, mice and songbirds. The convergence of data from the behavioural, neuroimaging, and gene expression studies lead to a tentative model of the neuroanatomy of the speech and language system.
The neuropsychological and neuroimaging findings will be related to the genetic basis of the disorder in the KE family and to that of other cases with mutations and/or deletions of the FOXP2 gene, and to the pattern of gene expression during embryological development in humans, mice and songbirds. The convergence of data from the behavioural, neuroimaging, and gene expression studies lead to a tentative model of the neuroanatomy of the speech and language system.