Abstract
To identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in imparied visuospatial constructive cognition.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Blotting, Northern
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Brain / embryology
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Brain / growth & development
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Brain / physiology
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Chromosome Aberrations
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Chromosomes, Human, Pair 7 / genetics
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Cognition / physiology*
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DNA-Binding Proteins / genetics*
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Elastin / genetics
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Gene Deletion
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Gene Expression Regulation, Developmental / physiology
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Humans
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In Situ Hybridization, Fluorescence
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Lim Kinases
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Molecular Sequence Data
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Phenotype
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Protein Kinases / genetics
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Protein Serine-Threonine Kinases / genetics*
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Sequence Analysis, DNA
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Visual Perception / genetics*
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Williams Syndrome / genetics*
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Zinc Fingers / genetics
Substances
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DNA-Binding Proteins
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Elastin
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Protein Kinases
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LIMK1 protein, human
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Lim Kinases
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Protein Serine-Threonine Kinases
Associated data
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GENBANK/U62292
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GENBANK/U62293