Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome.
Little is known about genetic regulation of the development of white matter. This knowledge is critical in understanding the pathophysiology of neurodevelopmental syndromes associated with altered cognition as well as in elucidating the genetics of normal human cognition. The hemideletion of approximately 25 genes on chromosome 7q11.23 that causes Williams syndrome (WS) includes genes that regulate cytoskeletal dynamics in neurons, especially LIMK1 and CYLN2, and therefore offers the opportunity to investigate the role of these genes in the formation of white matter tracts. We used diffusion tensor imaging to demonstrate alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence in WS. These abnormalities are consistent with an alteration of the late stages of neuronal migration, define alterations of white matter structures underlying dissociable behavioral phenotypes in WS, and provide human in vivo information about genetic control of white matter tract formation.
Marenco
Stefano
S
Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA. marencos@mail.nih.gov
Siuta
Michael A
MA
Kippenhan
J Shane
JS
Grodofsky
Samuel
S
Chang
Wei-Li
WL
Kohn
Philip
P
Mervis
Carolyn B
CB
Morris
Colleen A
CA
Weinberger
Daniel R
DR
Meyer-Lindenberg
Andreas
A
Pierpaoli
Carlo
C
Berman
Karen Faith
KF
D000328:Adult; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D018980:Williams Syndrome / Q000235:genetics* / Q000473:pathology*