Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.
The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected.
Belton
Emma
E
Developmental Cognitive Neuroscience Unit, Institute of Child Health, University College London, Great Ormond Street Hospital for Children, NHS Trust, The Wolson Centre, Mecklenburgh Square, London, United Kingdom. E.Belton@ich.ucl.ac.uk
Salmond
Claire H
CH
Watkins
Kate E
KE
Vargha-Khadem
Faraneh
F
Gadian
David G
DG
D000293:Adolescent; D001072:Apraxias / Q000235:genetics / Q000473:pathology*; D002421:Caudate Nucleus / Q000002:abnormalities* / Q000473:pathology*; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors; D007839:Functional Laterality / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017354:Point Mutation; D013064:Speech Disorders / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics
C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors