Human Genetic Disorders of Axon Guidance

Department of Neurology, FM Kirby Neurobiology Center, Program in Genomics, Children's Hospital Boston, Massachusetts 02115-5737, USA.
Cold Spring Harbor perspectives in biology (Impact Factor: 8.68). 03/2010; 2(3):a001784. DOI: 10.1101/cshperspect.a001784
Source: PubMed


This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive scoliosis, Kallmann syndrome, albinism, congenital fibrosis of the extraocular muscles type 1, Duane retraction syndrome, and pontine tegmental cap dysplasia. Genes mutated in these disorders can encode axon growth cone ligands and receptors, downstream signaling molecules, and axon transport motors, as well as proteins without currently recognized roles in axon guidance. Advances in neuroimaging and genetic techniques have the potential to rapidly expand this field, and it is feasible that axon guidance disorders will soon be recognized as a new and significant category of human neurodevelopmental disorders.

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    • "The cortical innervation defects that occur in the absence of Slit/Robo signaling in mice resemble defects present in mouse models of Down syndrome [2], [3]. Moreover, defects in Slit/Robo signaling disrupt commissural axon crossing in the hindbrain in horizontal gaze palsy with progressive scoliosis [4], [5]. The Slit/Robo signaling pathway is also associated with early infantile epileptic encephalopathy [6] and autism [7]. "
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