LIM-KINASE1 HEMIZYGOSITY IMPLICATED IN IMPAIRED VISUOSPATIAL CONSTRUCTIVE COGNITION

To identify genes important for human cognitive development, we studie d Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families wit h a partial WS phenotype; affected members have the specific WS cognit ive profile and vascular disease, but lack other WS features. Submicro scopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the sm allest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-ki nase-1 (LIMK1). The latter encodes a novel protein kinase with LIM dom ains and is strongly expressed in the brain. Because ELN mutations cau se vascular disease but not cognitive abnormalities, these data implic ate LIMK1 hemizygosity in impaired visuospatial constructive cognition .