1. DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus callosum, and developmental split brain syndrome
- Author
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Marsh, Ashley PL, Edwards, Timothy J, Galea, Charles, Cooper, Helen M, Engle, Elizabeth C, Jamuar, Saumya S, Méneret, Aurélie, Moutard, Marie‐Laure, Nava, Caroline, Rastetter, Agnès, Robinson, Gail, Rouleau, Guy, Roze, Emmanuel, Spencer‐Smith, Megan, Trouillard, Oriane, de Villemeur, Thierry Billette, Walsh, Christopher A, Yu, Timothy W, Consortium, IRC5, Heron, Delphine, Sherr, Elliott H, Richards, Linda J, Depienne, Christel, Leventer, Richard J, and Lockhart, Paul J
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Genetics ,Digestive Diseases ,Brain Disorders ,Neurosciences ,Pediatric ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Abnormalities ,Multiple ,Agenesis of Corpus Callosum ,Amino Acid Sequence ,Binding Sites ,Conserved Sequence ,Databases ,Genetic ,Genes ,DCC ,Genetic Association Studies ,Humans ,Magnetic Resonance Imaging ,Models ,Molecular ,Mutation ,Netrin-1 ,Phenotype ,Protein Binding ,Protein Conformation ,Protein Domains ,Syndrome ,ACC ,agenesis of the corpus callosum ,axon guidance ,DCC ,developmental split brain syndrome ,horizontal gaze palsy with progressive scoliosis ,mirror movements ,mutation ,NTN1 ,IRC5 Consortium ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
The deleted in colorectal cancer (DCC) gene encodes the netrin-1 (NTN1) receptor DCC, a transmembrane protein required for the guidance of commissural axons. Germline DCC mutations disrupt the development of predominantly commissural tracts in the central nervous system (CNS) and cause a spectrum of neurological disorders. Monoallelic, missense, and predicted loss-of-function DCC mutations cause congenital mirror movements, isolated agenesis of the corpus callosum (ACC), or both. Biallelic, predicted loss-of-function DCC mutations cause developmental split brain syndrome (DSBS). Although the underlying molecular mechanisms leading to disease remain poorly understood, they are thought to stem from reduced or perturbed NTN1 signaling. Here, we review the 26 reported DCC mutations associated with abnormal CNS development in humans, including 14 missense and 12 predicted loss-of-function mutations, and discuss their associated clinical characteristics and diagnostic features. We provide an update on the observed genotype-phenotype relationships of congenital mirror movements, isolated ACC and DSBS, and correlate this to our current understanding of the biological function of DCC in the development of the CNS. All mutations and their associated phenotypes were deposited into a locus-specific LOVD (https://databases.lovd.nl/shared/genes/DCC).
- Published
- 2018