Abstract
Mirror movements are involuntary contralateral movements that mirror voluntary ones and are often associated with defects in midline crossing of the developing central nervous system. We studied two large families, one French Canadian and one Iranian, in which isolated congenital mirror movements were inherited as an autosomal dominant trait. We found that affected individuals carried protein-truncating mutations in DCC (deleted in colorectal carcinoma), a gene on chromosome 18q21.2 that encodes a receptor for netrin-1, a diffusible protein that helps guide axon growth across the midline. Functional analysis of the mutant DCC protein from the French Canadian family revealed a defect in netrin-1 binding. Thus, DCC has an important role in lateralization of the human nervous system.
MeSH terms
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Axons / physiology
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Codon, Terminator
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DCC Receptor
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Dyskinesias / congenital*
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Dyskinesias / genetics*
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Female
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Frameshift Mutation*
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Functional Laterality
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Genes, DCC*
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Genes, Dominant
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Genome-Wide Association Study
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Haplotypes
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Humans
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Male
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Mutant Proteins / chemistry
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Mutant Proteins / metabolism
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Nerve Growth Factors / metabolism
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Nervous System / growth & development
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Netrin-1
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Pedigree
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Protein Binding
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Tumor Suppressor Proteins / chemistry
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism*
Substances
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Codon, Terminator
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DCC Receptor
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DCC protein, human
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Mutant Proteins
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NTN1 protein, human
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Nerve Growth Factors
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Receptors, Cell Surface
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Tumor Suppressor Proteins
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Netrin-1